Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics
Identifieur interne : 000B08 ( Pmc/Curation ); précédent : 000B07; suivant : 000B09Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics
Auteurs : Rayana L. Bighetti-Trevisan [Brésil] ; Lucas O. Sousa [Brésil] ; Rogerio M. Castilho [États-Unis] ; Luciana O. Almeida [Brésil]Source :
- Stem Cells International [ 1687-966X ] ; 2019.
Abstract
A frequent observation in several malignancies is the development of resistance to therapy that results in frequent tumor relapse and metastasis. Much of the tumor resistance phenotype comes from its heterogeneity that halts the ability of therapeutic agents to eliminate all cancer cells effectively. Tumor heterogeneity is, in part, controlled by cancer stem cells (CSC). CSC may be considered the reservoir of cancer cells as they exhibit properties of self-renewal and plasticity and the capability of reestablishing a heterogeneous tumor cell population. The endowed resistance mechanisms of CSC are mainly attributed to several factors including cellular quiescence, accumulation of ABC transporters, disruption of apoptosis, epigenetic reprogramming, and metabolism. There is a current need to develop new therapeutic drugs capable of targeting CSC to overcome tumor resistance. Emerging in vitro and in vivo studies strongly support the potential benefits of combination therapies capable of targeting cancer stem cell-targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This review will address the main characteristics, therapeutic implications, and perspectives of targeting CSC to improve current anticancer therapeutics.
Url:
DOI: 10.1155/2019/9618065
PubMed: 31781251
PubMed Central: 6874936
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics</title><author><name sortKey="Bighetti Trevisan, Rayana L" sort="Bighetti Trevisan, Rayana L" uniqKey="Bighetti Trevisan R" first="Rayana L." last="Bighetti-Trevisan">Rayana L. Bighetti-Trevisan</name><affiliation wicri:level="1"><nlm:aff id="I1">Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904</wicri:regionArea></affiliation></author><author><name sortKey="Sousa, Lucas O" sort="Sousa, Lucas O" uniqKey="Sousa L" first="Lucas O." last="Sousa">Lucas O. Sousa</name><affiliation wicri:level="1"><nlm:aff id="I2">Laboratory of Markers and Cell Signaling of Cancer, Department of Clinical Analyses, Toxicology and Food Sciences, University of Sao Paulo School of Pharmaceutical Sciences, Ribeirao Preto, SP 14040-903, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Markers and Cell Signaling of Cancer, Department of Clinical Analyses, Toxicology and Food Sciences, University of Sao Paulo School of Pharmaceutical Sciences, Ribeirao Preto, SP 14040-903</wicri:regionArea></affiliation></author><author><name sortKey="Castilho, Rogerio M" sort="Castilho, Rogerio M" uniqKey="Castilho R" first="Rogerio M." last="Castilho">Rogerio M. Castilho</name><affiliation wicri:level="1"><nlm:aff id="I3">Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078</wicri:regionArea></affiliation></author><author><name sortKey="Almeida, Luciana O" sort="Almeida, Luciana O" uniqKey="Almeida L" first="Luciana O." last="Almeida">Luciana O. Almeida</name><affiliation wicri:level="1"><nlm:aff id="I1">Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31781251</idno><idno type="pmc">6874936</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874936</idno><idno type="RBID">PMC:6874936</idno><idno type="doi">10.1155/2019/9618065</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B08</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B08</idno><idno type="wicri:Area/Pmc/Curation">000B08</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B08</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics</title><author><name sortKey="Bighetti Trevisan, Rayana L" sort="Bighetti Trevisan, Rayana L" uniqKey="Bighetti Trevisan R" first="Rayana L." last="Bighetti-Trevisan">Rayana L. Bighetti-Trevisan</name><affiliation wicri:level="1"><nlm:aff id="I1">Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904</wicri:regionArea></affiliation></author><author><name sortKey="Sousa, Lucas O" sort="Sousa, Lucas O" uniqKey="Sousa L" first="Lucas O." last="Sousa">Lucas O. Sousa</name><affiliation wicri:level="1"><nlm:aff id="I2">Laboratory of Markers and Cell Signaling of Cancer, Department of Clinical Analyses, Toxicology and Food Sciences, University of Sao Paulo School of Pharmaceutical Sciences, Ribeirao Preto, SP 14040-903, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Markers and Cell Signaling of Cancer, Department of Clinical Analyses, Toxicology and Food Sciences, University of Sao Paulo School of Pharmaceutical Sciences, Ribeirao Preto, SP 14040-903</wicri:regionArea></affiliation></author><author><name sortKey="Castilho, Rogerio M" sort="Castilho, Rogerio M" uniqKey="Castilho R" first="Rogerio M." last="Castilho">Rogerio M. Castilho</name><affiliation wicri:level="1"><nlm:aff id="I3">Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078</wicri:regionArea></affiliation></author><author><name sortKey="Almeida, Luciana O" sort="Almeida, Luciana O" uniqKey="Almeida L" first="Luciana O." last="Almeida">Luciana O. Almeida</name><affiliation wicri:level="1"><nlm:aff id="I1">Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904</wicri:regionArea></affiliation></author></analytic><series><title level="j">Stem Cells International</title><idno type="ISSN">1687-966X</idno><idno type="eISSN">1687-9678</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A frequent observation in several malignancies is the development of resistance to therapy that results in frequent tumor relapse and metastasis. Much of the tumor resistance phenotype comes from its heterogeneity that halts the ability of therapeutic agents to eliminate all cancer cells effectively. Tumor heterogeneity is, in part, controlled by cancer stem cells (CSC). CSC may be considered the reservoir of cancer cells as they exhibit properties of self-renewal and plasticity and the capability of reestablishing a heterogeneous tumor cell population. The endowed resistance mechanisms of CSC are mainly attributed to several factors including cellular quiescence, accumulation of ABC transporters, disruption of apoptosis, epigenetic reprogramming, and metabolism. There is a current need to develop new therapeutic drugs capable of targeting CSC to overcome tumor resistance. Emerging in vitro and in vivo studies strongly support the potential benefits of combination therapies capable of targeting cancer stem cell-targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This review will address the main characteristics, therapeutic implications, and perspectives of targeting CSC to improve current anticancer therapeutics.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Colombet, M" uniqKey="Colombet M">M. Colombet</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lytle, N K" uniqKey="Lytle N">N. K. Lytle</name></author><author><name sortKey="Barber, A G" uniqKey="Barber A">A. G. Barber</name></author><author><name sortKey="Reya, T" uniqKey="Reya T">T. Reya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kreso, A" uniqKey="Kreso A">A. 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Rachagani</name></author><author><name sortKey="Qazi, A K" uniqKey="Qazi A">A. K. Qazi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Stem Cells Int</journal-id><journal-id journal-id-type="iso-abbrev">Stem Cells Int</journal-id><journal-id journal-id-type="publisher-id">SCI</journal-id><journal-title-group><journal-title>Stem Cells International</journal-title></journal-title-group><issn pub-type="ppub">1687-966X</issn><issn pub-type="epub">1687-9678</issn><publisher><publisher-name>Hindawi</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31781251</article-id><article-id pub-id-type="pmc">6874936</article-id><article-id pub-id-type="doi">10.1155/2019/9618065</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-0228-3652</contrib-id><name><surname>Bighetti-Trevisan</surname><given-names>Rayana L.</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-8234-2746</contrib-id><name><surname>Sousa</surname><given-names>Lucas O.</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0001-5358-612X</contrib-id><name><surname>Castilho</surname><given-names>Rogerio M.</given-names></name><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-5342-0434</contrib-id><name><surname>Almeida</surname><given-names>Luciana O.</given-names></name><email>lubio2001@usp.br</email><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Laboratory of Tissue Culture, Department of Basic and Oral Biology, University of Sao Paulo School of Dentistry, Ribeirao Preto, SP 14040-904, Brazil</aff><aff id="I2"><sup>2</sup>Laboratory of Markers and Cell Signaling of Cancer, Department of Clinical Analyses, Toxicology and Food Sciences, University of Sao Paulo School of Pharmaceutical Sciences, Ribeirao Preto, SP 14040-903, Brazil</aff><aff id="I3"><sup>3</sup>Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA</aff><author-notes><fn fn-type="other"><p>Academic Editor: Sumanta Chatterjee</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>12</day><month>11</month><year>2019</year></pub-date><volume>2019</volume><elocation-id>9618065</elocation-id><history><date date-type="received"><day>22</day><month>7</month><year>2019</year></date><date date-type="rev-recd"><day>25</day><month>9</month><year>2019</year></date><date date-type="accepted"><day>3</day><month>10</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Rayana L. Bighetti-Trevisan et al.</copyright-statement><copyright-year>2019</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>A frequent observation in several malignancies is the development of resistance to therapy that results in frequent tumor relapse and metastasis. Much of the tumor resistance phenotype comes from its heterogeneity that halts the ability of therapeutic agents to eliminate all cancer cells effectively. Tumor heterogeneity is, in part, controlled by cancer stem cells (CSC). CSC may be considered the reservoir of cancer cells as they exhibit properties of self-renewal and plasticity and the capability of reestablishing a heterogeneous tumor cell population. The endowed resistance mechanisms of CSC are mainly attributed to several factors including cellular quiescence, accumulation of ABC transporters, disruption of apoptosis, epigenetic reprogramming, and metabolism. There is a current need to develop new therapeutic drugs capable of targeting CSC to overcome tumor resistance. Emerging in vitro and in vivo studies strongly support the potential benefits of combination therapies capable of targeting cancer stem cell-targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This review will address the main characteristics, therapeutic implications, and perspectives of targeting CSC to improve current anticancer therapeutics.</p></abstract><funding-group><award-group><funding-source>Fundação de Amparo à Pesquisa do Estado de São Paulo</funding-source><award-id>2018/02959-7</award-id><award-id>2017/11780-8</award-id></award-group></funding-group></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Targeting cancer stem cells signaling to overcome resistance of current anticancer therapy. While the conventional chemotherapy and radiotherapy eliminate more differentiated cancer cells, specific phenotypes of CSC (i.e., multidrug resistance, epigenetic reprogramming, and tumor microenvironment protection) allow them to evade the conventional treatments and avoid the cell death. Once CSC population accumulates, after conventional therapy, they start to regrowth the tumor promoting cancer recurrence. To avoid recurrence, a more efficient therapeutic regimen purposes the administration of new drugs that directly target CSC metabolism, self-renewal, differentiation or other stem cell particularities to disrupt CSC, concomitant with conventional therapies to eliminate differentiated cells.</p></caption><graphic xlink:href="SCI2019-9618065.001"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Clinical trials involving combination treatment targeting cancer stem cells to overcome chemo- and radioresistance.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Tumor type</th><th align="center" rowspan="1" colspan="1">Clinical trial ID</th><th align="center" rowspan="1" colspan="1">Drug targeting CSC (plus chemo/radiotherapy)</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Breast</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02876302?term=NCT02876302&draw=2&rank=1">NCT02876302</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02776917?term=NCT02776917&draw=2&rank=1">NCT02776917</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02370238?term=NCT02370238&draw=2&rank=1">NCT02370238</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01868503?term=NCT01868503&draw=2&rank=1">NCT01868503</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01876251?term=NCT01876251&draw=2&rank=1">NCT01876251</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02001974?term=NCT02001974&draw=2&rank=1">NCT02001974</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01372579?term=NCT01372579&draw=2&rank=1">NCT01372579</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01281163?term=NCT01281163&draw=2&rank=1">NCT01281163</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01190345?term=NCT01190345&draw=2&rank=1">NCT01190345</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01118975?term=NCT01118975&draw=2&rank=1">NCT01118975</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00949247?term=NCT00949247&draw=2&rank=1">NCT00949247</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00645333?term=NCT00645333&draw=2&rank=1">NCT00645333</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00524303?term=NCT00524303&draw=2&rank=1">NCT00524303</ext-link></td><td align="center" rowspan="1" colspan="1">Ruxolitinib; cirmtuzumab; reparixin; lapatinib; PF-03084014; eribulin mesylate; MK2206; bevacizumab; vorinostat; MK0752; trastuzumab</td></tr><tr><td align="left" rowspan="1" colspan="1">Pancreatic</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02231723?term=NCT02231723&draw=2&rank=1">NCT022311723</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01195415?term=NCT01195415&draw=2&rank=1">NCT01195415</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01192763?term=NCT01192763&draw=2&rank=1">NCT01192763</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01189929?term=NCT01189929&draw=2&rank=1">NCT01189929</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01051284?term=NCT01051284&draw=2&rank=1">NCT01051284</ext-link></td><td align="center" rowspan="1" colspan="1">BBI608; vismodegib; RO4929097; demcizumab; cyberknife radiation</td></tr><tr><td align="left" rowspan="1" colspan="1">Ovarian</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03632798?term=NCT03632798&draw=2&rank=1">NCT03632798</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03030287?term=NCT03030287&draw=2&rank=1">NCT03030287</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02713386?term=NCT02713386&draw=2&rank=1">NCT02713386</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01579812?term=NCT01579812&draw=2&rank=1">NCT01579812</ext-link></td><td align="center" rowspan="1" colspan="1">Avastin; OMP-305B83; ruxolitinib; metformin</td></tr><tr><td align="left" rowspan="1" colspan="1">Hematologic</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03113643?term=NCT03113643&draw=2&rank=1">NCT03113643</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02730195?term=NCT02730195&draw=2&rank=1">NCT02730195</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01861340?term=NCT01861340&draw=2&rank=1">NCT01861340</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01130688?term=NCT01130688&draw=2&rank=1">NCT01130688</ext-link></td><td align="center" rowspan="1" colspan="1">Azacitidine; pioglitazone; MEDI-551; zileuton</td></tr><tr><td align="left" rowspan="1" colspan="1">Glioma</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03632135?term=NCT03632135&draw=2&rank=1">NCT03632135</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02315534?term=NCT02315534&draw=2&rank=1">NCT02315534</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02039778?term=NCT02039778&draw=2&rank=1">NCT02039778</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01119599?term=NCT01119599&draw=2&rank=1">NCT01119599</ext-link></td><td align="center" rowspan="1" colspan="1">Vincristine; irinotecan; etoposide; imatinib; BBI608; stem cell radiotherapy; RO4929097</td></tr><tr><td align="left" rowspan="1" colspan="1">Colorectal</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03035253?term=NCT03035253&draw=2&rank=1">NCT03035253</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02753127?term=NCT02753127&draw=2&rank=1">NCT02753127</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01189942?term=NCT01189942&draw=2&rank=1">NCT01189942</ext-link></td><td align="center" rowspan="1" colspan="1">OMP-305B83; BBI608; OMP-21M18</td></tr><tr><td align="left" rowspan="1" colspan="1">Non-small-cell lung</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01193868?term=NCT01193868&draw=2&rank=1">NCT01193868</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01189968?term=NCT01189968&draw=2&rank=1">NCT01189968</ext-link></td><td align="center" rowspan="1" colspan="1">RO4929097; demcizumab</td></tr><tr><td align="left" rowspan="1" colspan="1">Hepatocellular</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02279719?term=NCT02279719&draw=2&rank=1">NCT02279719</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01442870?term=NCT01442870&draw=2&rank=1">NCT01442870</ext-link></td><td align="center" rowspan="1" colspan="1">BBI503; BBI608; metformin</td></tr><tr><td align="left" rowspan="1" colspan="1">Esophageal</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02423811?term=NCT02423811&draw=2&rank=1">NCT02423811</ext-link></td><td align="center" rowspan="1" colspan="1">Fursultiamine</td></tr><tr><td align="left" rowspan="1" colspan="1">Gastrointestinal</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02024607?term=NCT02024607&draw=2&rank=1">NCT02024607</ext-link></td><td align="center" rowspan="1" colspan="1">BBI608</td></tr><tr><td align="left" rowspan="1" colspan="1">Head and neck</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01255800?term=NCT01255800&draw=2&rank=1">NCT01255800</ext-link></td><td align="center" rowspan="1" colspan="1">IPI-926</td></tr><tr><td align="left" rowspan="1" colspan="1">Advanced or metastatic</td><td align="center" rowspan="1" colspan="1"><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02722954?term=NCT02722954&draw=2&rank=1">NCT02722954</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02483247?term=NCT02483247&draw=2&rank=1">NCT02483247</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02467361?term=NCT02467361&draw=2&rank=1">NCT02467361</ext-link>; <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02432326?term=NCT02432326&draw=2&rank=1">NCT02432326</ext-link></td><td align="center" rowspan="1" colspan="1">Demcizumab; BBI503; BBI608</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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