Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness
Identifieur interne : 000A13 ( Ncbi/Merge ); précédent : 000A12; suivant : 000A14Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness
Auteurs : Kha-Liang Lee [Taïwan] ; Yung-Che Kuo [Taïwan] ; Yuan-Soon Ho [Taïwan] ; Yen-Hua Huang [Taïwan]Source :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%–20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell–like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted.
Url:
DOI: 10.3390/cancers11091334
PubMed: 31505803
PubMed Central: 6769912
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(Y.-C.K.)</nlm:aff><wicri:noCountry code="subfield">Taiwan (K.-L.L.) 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TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell–like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancers (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Cancers (Basel)</journal-id><journal-id journal-id-type="publisher-id">cancers</journal-id><journal-title-group><journal-title>Cancers</journal-title></journal-title-group><issn pub-type="epub">2072-6694</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31505803</article-id><article-id pub-id-type="pmc">6769912</article-id><article-id pub-id-type="doi">10.3390/cancers11091334</article-id><article-id pub-id-type="publisher-id">cancers-11-01334</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-1579-3384</contrib-id><name><surname>Lee</surname><given-names>Kha-Liang</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01334">1</xref><xref ref-type="aff" rid="af2-cancers-11-01334">2</xref><xref ref-type="author-notes" rid="fn1-cancers-11-01334">†</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-9425-7389</contrib-id><name><surname>Kuo</surname><given-names>Yung-Che</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01334">1</xref><xref ref-type="aff" rid="af3-cancers-11-01334">3</xref><xref ref-type="aff" rid="af4-cancers-11-01334">4</xref><xref ref-type="author-notes" rid="fn1-cancers-11-01334">†</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-3649-6680</contrib-id><name><surname>Ho</surname><given-names>Yuan-Soon</given-names></name><xref ref-type="aff" rid="af2-cancers-11-01334">2</xref><xref ref-type="aff" rid="af4-cancers-11-01334">4</xref><xref ref-type="aff" rid="af5-cancers-11-01334">5</xref><xref rid="c1-cancers-11-01334" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-6020-9998</contrib-id><name><surname>Huang</surname><given-names>Yen-Hua</given-names></name><xref ref-type="aff" rid="af1-cancers-11-01334">1</xref><xref ref-type="aff" rid="af2-cancers-11-01334">2</xref><xref ref-type="aff" rid="af3-cancers-11-01334">3</xref><xref ref-type="aff" rid="af4-cancers-11-01334">4</xref><xref ref-type="aff" rid="af6-cancers-11-01334">6</xref><xref ref-type="aff" rid="af7-cancers-11-01334">7</xref><xref ref-type="aff" rid="af8-cancers-11-01334">8</xref><xref ref-type="aff" rid="af9-cancers-11-01334">9</xref><xref rid="c1-cancers-11-01334" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cancers-11-01334"><label>1</label>Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan (K.-L.L.) (Y.-C.K.)</aff><aff id="af2-cancers-11-01334"><label>2</label>Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af3-cancers-11-01334"><label>3</label>TMU Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af4-cancers-11-01334"><label>4</label>TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af5-cancers-11-01334"><label>5</label>School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af6-cancers-11-01334"><label>6</label>International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af7-cancers-11-01334"><label>7</label>Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af8-cancers-11-01334"><label>8</label>Comprehensive Cancer Center of Taipei Medical University, Taipei 11031, Taiwan</aff><aff id="af9-cancers-11-01334"><label>9</label>Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan</aff><author-notes><corresp id="c1-cancers-11-01334"><label>*</label>Correspondence: <email>hoyuansn@tmu.edu.tw</email> (Y.-S.H.); <email>rita1204@tmu.edu.tw</email> (Y.-H.H.); Tel.: +886-2-2736-1661 (Ext. 3327) (Y.-S.H.); +886-2-2736-1661 (Ext. 3150) (Y.-H.H.)</corresp><fn id="fn1-cancers-11-01334"><label>†</label><p>The authors contributed equally to this article.</p></fn></author-notes><pub-date pub-type="epub"><day>09</day><month>9</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>9</month><year>2019</year></pub-date><volume>11</volume><issue>9</issue><elocation-id>1334</elocation-id><history><date date-type="received"><day>02</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>30</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%–20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell–like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted.</p></abstract><kwd-group><kwd>TNBC</kwd><kwd>Recurrence</kwd><kwd>Resistance</kwd><kwd>Cancer stem cell</kwd><kwd>IGF-1R</kwd><kwd>nAChR</kwd></kwd-group></article-meta></front><floats-group><fig id="cancers-11-01334-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Diagram of ongoing clinical trials in TNBCs. (<bold>A</bold>) System view of signaling pathways activated by extracellular stimuli, which triggered multiple biological functions through central hub AKT or subsequent effectors. Numerous inhibitors attempt to attack these critical molecules in TNBCs, and ongoing phases of clinical trials for categorized inhibitors have also revealed the same. (<bold>B</bold>) Disruption of cell cycle by CDK inhibitors in TNBC trials. (<bold>C</bold>) Blockade of immune checkpoints in cancer immunotherapy. Prevention of PD-1/PD-L1 signaling transduction from inhibitors could activate CD8<sup>+</sup> T cells to kill TNBC tumor cells.</p></caption><graphic xlink:href="cancers-11-01334-g001"></graphic></fig><fig id="cancers-11-01334-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Diagram of ongoing clinical trials of potential targeting strategies against CSCs in carcinoma. System view of signaling pathways activated by extracellular stimuli, which triggered multiple biological functions through subsequent effectors. Numerous inhibitors and inducer attempt to attack either these critical molecules or pathways in CSCs in several types of carcinoma.</p></caption><graphic xlink:href="cancers-11-01334-g002"></graphic></fig><fig id="cancers-11-01334-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Diagram of molecular pathways involving in CSC drug resistance. System view of drug resistance, which triggered by multiple pathways through subsequent effectors. Some effectors can cross-talk to other molecules leading to stimulate different biological functions, which cooperatively play roles in drug resistance in CSCs. EMT: epithelial-mesenchymal transition; SDR: spontaneous drug resistance; CTC: circulating tumor cell; UPR: unfolded protein response; ERS: endoplasmic reticulum stress; DDR: DNA damage response; ROS: reactive oxygen species; CAF: cancer-associated fibroblast.</p></caption><graphic xlink:href="cancers-11-01334-g003"></graphic></fig><table-wrap id="cancers-11-01334-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-11-01334-t001_Table 1</object-id><label>Table 1</label><caption><p>The ongoing clinical trials in triple-negative breast cancer.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Major Drug</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Combinational Drug</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Phase</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">NCT Identifiers</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Status <sup>#</sup></th></tr></thead><tbody><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>BRCA1/2</bold></td></tr><tr><td rowspan="24" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">PARP</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">BGB290</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Temozolomide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03150810</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="4" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">BMN-673</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02401347</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02358200</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± CB-839 (GLS1i)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03875313</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± ZEN003694 (BETi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03901469</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Niraparib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Pembrolizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02657889</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="12" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Olaparib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT00679783</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± AZD2014 (mTORi) ± AZD5363 (AKTi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02208375</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± AZD6738 ± AZD1775</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03330847</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± BKM120 (PI3Ki) ± BYL719 (PI3Ki)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01623349</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT00516724</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II/III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03150576</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cediranib (VGEFi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01116648</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cediranib ± Durvalumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02484404</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Durvalumab (anti PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03544125</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Durvalumab (anti PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03801369</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Durvalumab (anti PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03167619</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Onalespib (HSP90i)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02898207</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rucaparib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cisplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01074970</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="5" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Veliparib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin ± Cyclophosphamide ± Doxorubicin ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01818063</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin ± Cyclophosphamide ± Doxorubicin ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02032277</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cisplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02595905</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Irinotecan Hydrochloride</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT00576654</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Lapatinib (EGFR/HER2i)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pilot study</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02158507</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>CHK1 and WEE1</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CHK1</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LY2880070</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gemcitabine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I /II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02632448</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CHK1/2</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LY2606368</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02203513</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">WEE1</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">AZD1775</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02482311</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cisplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03012477</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Cyclin-dependent kinases</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td rowspan="5" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">CDKs</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Abemaciclib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03130439</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PF-06873600</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Endocrine Therapy</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03519178</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ribociclib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Bicalutamide (ARi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03090165</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SHR6390</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± SHR3680 (ARi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03805399</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Trilaciclib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gemcitabine + Carboplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02978716</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Androgen receptor</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td rowspan="7" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Androgen</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bicalutamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03055312</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CR1447(ARM)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02067741</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Darolutamide (NSAA)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Capecitabine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03383679</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Enzalutamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02750358</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01889238</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02689427</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">GTx-024 (SARM)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Pambrolizumab (anti PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02971761</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Growth factors and angiogenesis</bold></td></tr><tr><td rowspan="6" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">EGFR</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cetuximab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Ixabepilone</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01097642</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Icotinib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02362230</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Panitumumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gemcitabine + Cisplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02546934</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02593175</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Paclitaxel + Doxorubicin + Cyclophosphamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02876107</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SCT200</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03692689</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HER2</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Trastuzumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel + Cyclophosphamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01750073</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEGF</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bevacizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel + Erlotinib (EGFRi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT00733408</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">VEGFR2</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Apatinib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Fluzoparib (PARPi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03075462</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Vinorelbine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03254654</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>SRC and WNT signaling</bold></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SRC</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dasatinib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02720185</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">WNT</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">LGK974</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± PDR001 (anti-PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01351103</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gedatolisib (PI3Ki)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03243331</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>PI3K/AKT/mTOR pathway</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PIK3CA</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Taselisib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Enzalutamide (ARi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02457910</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">PIK3CB</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IPI-549</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Nivolumab (anti PD-1)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02637531</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PQR309</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Eribulin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02723877</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="4" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">PI3K</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">AZD8186</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01884285</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Docetaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03218826</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">BKM120</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Capecitabine + Trastuzumab (HER2i)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02000882</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CUDC-907</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02307240</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="6" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">AKT</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ARQ092</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02476955</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AZD5363</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02423603</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">GSK2141795</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Trametinib (MEKi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01964924</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Ipatasertib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02162719</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03853707</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II/III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03337724</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="6" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">mTOR</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AZD2014</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Selumetinib (ERKi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02583542</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Everolimus</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cisplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02120469</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Cisplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02531932</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Doxorubicin + Bevacizumab (VEGFi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02456857</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Gedatolisib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Docetaxel + Cisplatin + Dacomitinib (EGFRi)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01920061</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Tak-117 (PI3Ki) + Cisplatin + Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03193853</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td colspan="6" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Immune checkpoint</bold></td></tr><tr><td rowspan="15" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">PD-1</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Nivolumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Capecitabine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03487666</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03414684</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PDR001</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02404441</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="11" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Pembrolizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03197389</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02447003</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02644369</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02555657</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Capecitabine ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02734290</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Doxorubicin ± Aromatase inhibitors</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02648477</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Nab-paclitaxel (or Paclitaxel) + Carboplatin + Doxorubicin + Cyclophosphamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02622074</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Nab-paclitaxel (or Paclitaxel) ± Gemcitabine + Carboplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02819518,</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel + Carboplatin ± Doxorubicin ± Epirubicin + Cyclophosphamide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03036488</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Lenvatinib (TKI)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03797326</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± PVX-410 Vaccine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03362060</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SHR1210</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Apatinib (TKI)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03394287</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="6" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">PD-L1</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Atezolizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03206203</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Cyclophosphamide ± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT01898117</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Durvalumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Oleclumab + Paclitaxel + Carboplatin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT03616886</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02628132</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02685059</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FAZ053</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± PDR001</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT02936102</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr></tbody></table><table-wrap-foot><fn><p>#, R: recruiting; Ac/NR: active, not recruiting.</p></fn></table-wrap-foot></table-wrap><table-wrap id="cancers-11-01334-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-11-01334-t002_Table 2</object-id><label>Table 2</label><caption><p>The ongoing clinical trials of potential targeting molecules in carcinoma diseases.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Major Drug</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Combinational Drug</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Indication</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Phase</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">NCT Identifiers</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Status <sup>#</sup></th></tr></thead><tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Receptor</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td rowspan="9" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">IGF-1R</td><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">AMG479 (Ganitumab)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Dasatinb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Embryonal and alveolar rhabdomyo-sarcoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03041701 </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± (Everolimus + Panitumumab)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced solid tumors, NSCLC</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01061788</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Vincristine + Doxorubicin + Cyclo-phosphamide / Ifosfamide + Etoposide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Metastatic malignant neoplasm in the bone, bone marrow, lung, and etc.</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02306161</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Cixutumumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Lapatinib ditosylate + Capecitabine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-00684983</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Esophageal cancer, Gastro-esophageal junction adeno-carcinoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01142388</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DNA Plasmid Based Vaccine (WOKVAC)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02780401</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MK-0646 (Dalotuzumab)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gemcitabine + Erlotinib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced pancreatic cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-00769483 </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR </td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Teprotumumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Thyroid eye disease, Graves’ orbitopathy</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03298867</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Trastuzumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Lapatinib ditosylate</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01104571</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">nAChR</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bupropion</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03996265</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Cytokine</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IL-6 receptor</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tocilizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Ipilimumab + Nivolumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced melanoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03999749</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R </td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IL-7 receptor</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tocilizumab</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Gemcitabine + nab-Paclitaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Unresectable pancreatic carcinoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02767557 </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R </td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Dormancy and proliferation</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">All-trans retinoic acid (ATRA)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± 5-Azacitidine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prostate cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03572387</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R </td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Metabolism</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Glycolysis inhibition</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2-Deoxyglucose (2DG)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced cancer and hormone refractory prostate cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I/II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-00633087</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">T </td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Autophagy pathway</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td rowspan="3" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Autophagy inhibition</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hydro-chloroquine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01292408</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">U</td></tr><tr><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Chloroquine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">± Carboplatin + Gemcitabine</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced solid tumors</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02071537</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Temozolomide + Radiotherapy</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Glioblastoma multiforme</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02378532</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Drug resistance</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td rowspan="12" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Resistance inhibition</td><td rowspan="2" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Doxycycline</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bone-targeted therapy in patients with metastatic breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01847976</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">U</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cutaneous T-cell lymphoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02341209</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td rowspan="10" align="left" valign="middle" style="border-bottom:solid thin" colspan="1">Metformin</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Colon cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03359681</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prostate cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03137186</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Prostate cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02176161</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer prevention</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">III</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01905046</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Doxycycline</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast and uterine corpus cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02874430</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Erlotinib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">TNBC</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01650506</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">C</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Paclitaxel + Carboplatin + Docetaxel</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ovarian, primary peritoneal, or fallopian tube carcinoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-02122185</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Pembrolizumab </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Melanoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03311308</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Temozolomide</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Glioblastoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03243851</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ Temsirolimus</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Advanced cancers</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01529593</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td colspan="2" align="left" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Others</bold></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CD44</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RO5429083</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CD44-expressing, malignant solid tumors</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01358903</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">C</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ER</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tamoxifen </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ 9-Cis-retinoic acid</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-00001504</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">C</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">GD2</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3F8/GM-CSF</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ 13-Cis-retinoic acid</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Primary refractory neuroblastoma in bone marrow</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01183897</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ac/NR</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hedgehog</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vismodegib</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Basal cell carcinoma</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">II</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-03035188</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">R</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">+ RO4929097</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Breast cancer</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">I</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NCT-01071564</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">T</td></tr></tbody></table><table-wrap-foot><fn><p>#, R: recruiting; Ac/NR: active, not recruiting; T: terminated; U: unknown; C: completed; NR: not yet recruiting.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Lee, Kha Liang" sort="Lee, Kha Liang" uniqKey="Lee K" first="Kha-Liang" last="Lee">Kha-Liang Lee</name></noRegion><name sortKey="Ho, Yuan Soon" sort="Ho, Yuan Soon" uniqKey="Ho Y" first="Yuan-Soon" last="Ho">Yuan-Soon Ho</name><name sortKey="Ho, Yuan Soon" sort="Ho, Yuan Soon" uniqKey="Ho Y" first="Yuan-Soon" last="Ho">Yuan-Soon Ho</name><name sortKey="Ho, Yuan Soon" sort="Ho, Yuan Soon" uniqKey="Ho Y" first="Yuan-Soon" last="Ho">Yuan-Soon Ho</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Huang, Yen Hua" sort="Huang, Yen Hua" uniqKey="Huang Y" first="Yen-Hua" last="Huang">Yen-Hua Huang</name><name sortKey="Kuo, Yung Che" sort="Kuo, Yung Che" uniqKey="Kuo Y" first="Yung-Che" last="Kuo">Yung-Che Kuo</name><name sortKey="Kuo, Yung Che" sort="Kuo, Yung Che" uniqKey="Kuo Y" first="Yung-Che" last="Kuo">Yung-Che Kuo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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