Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer.
Identifieur interne : 001022 ( Main/Exploration ); précédent : 001021; suivant : 001023Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer.
Auteurs : Cheng Ji [République populaire de Chine] ; Li Zhang [États-Unis] ; Yan Cheng [États-Unis] ; Raj Patel [États-Unis] ; Hao Wu [États-Unis] ; Yi Zhang [États-Unis] ; Mian Wang [États-Unis] ; Shundong Ji [États-Unis] ; Chandra P. Belani [États-Unis] ; Jin-Ming Yang [États-Unis] ; Xingcong Ren [États-Unis]Source :
- Cancer biology & therapy [ 1555-8576 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Antinéoplasiques (pharmacologie), Autophagie (), Chloroquine (pharmacologie), Femelle, Humains, Hétérogreffes, Lignée cellulaire tumorale, Pyrazoles (pharmacologie), Pyridines (pharmacologie), Récepteurs à activité tyrosine kinase (génétique), Récepteurs à activité tyrosine kinase (métabolisme), Régulation négative, Résistance aux médicaments antinéoplasiques (), Souris nude, Sérine-thréonine kinases TOR (métabolisme), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- anatomopathologie : Tumeurs du poumon.
- génétique : Récepteurs à activité tyrosine kinase.
- métabolisme : Récepteurs à activité tyrosine kinase, Sérine-thréonine kinases TOR.
- pharmacologie : Antinéoplasiques, Chloroquine, Pyrazoles, Pyridines.
- traitement médicamenteux : Tumeurs du poumon.
- Animaux, Autophagie, Femelle, Humains, Hétérogreffes, Lignée cellulaire tumorale, Régulation négative, Résistance aux médicaments antinéoplasiques, Souris nude.
English descriptors
- KwdEn :
- Anaplastic Lymphoma Kinase, Animals, Antineoplastic Agents (pharmacology), Autophagy (drug effects), Cell Line, Tumor, Chloroquine (pharmacology), Crizotinib, Down-Regulation, Drug Resistance, Neoplasm (drug effects), Female, Heterografts, Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (pathology), Mice, Nude, Pyrazoles (pharmacology), Pyridines (pharmacology), Receptor Protein-Tyrosine Kinases (genetics), Receptor Protein-Tyrosine Kinases (metabolism), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , genetics : Receptor Protein-Tyrosine Kinases.
- chemical , metabolism : Receptor Protein-Tyrosine Kinases, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Antineoplastic Agents, Chloroquine, Pyrazoles, Pyridines.
- chemical : Anaplastic Lymphoma Kinase, Crizotinib.
- drug effects : Autophagy, Drug Resistance, Neoplasm.
- drug therapy : Lung Neoplasms.
- pathology : Lung Neoplasms.
- Animals, Cell Line, Tumor, Down-Regulation, Female, Heterografts, Humans, Mice, Nude.
Abstract
Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer. Nevertheless, acquired resistance to this drug occurs inevitably in approximately a year, limiting the therapeutic benefits of this novel targeted therapy. In this study, we found that autophagy was induced in crizonitib-resistant lung cancer cells and contributed to drug resistance. We observed that ALK was downregulated in the crizotinib-resistant lung cancer cell line, H3122CR-1, and this was causally associated with autophagy induction. The degree of crizotinib resistance correlated with autophagic activity. Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway. Furthermore, we demonstrated that chloroquine, an inhibitor of autophagy, could restore sensitivity of H3122CR-1 to crizotinib and enhance its efficacy against drug-resistant lung cancer. Thus, modulating autophagy may be worth exploring as a new strategy to overcome acquired crizonitib resistance in ALK-positive lung cancer.
DOI: 10.4161/cbt.28162
PubMed: 24556908
Affiliations:
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Hershey Medical Center; Hershey, PA USA; Department of Respiratory Medicine; The First Affiliated Hospital of Soochow University; Suzhou, Jiangsu, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA; Department of Respiratory Medicine; The First Affiliated Hospital of Soochow University; Suzhou, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Li" sort="Zhang, Li" uniqKey="Zhang L" first="Li" last="Zhang">Li Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Cheng, Yan" sort="Cheng, Yan" uniqKey="Cheng Y" first="Yan" last="Cheng">Yan Cheng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Patel, Raj" sort="Patel, Raj" uniqKey="Patel R" first="Raj" last="Patel">Raj Patel</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Zhang, Yi" sort="Zhang, Yi" uniqKey="Zhang Y" first="Yi" last="Zhang">Yi Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Wang, Mian" sort="Wang, Mian" uniqKey="Wang M" first="Mian" last="Wang">Mian Wang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Ji, Shundong" sort="Ji, Shundong" uniqKey="Ji S" first="Shundong" last="Ji">Shundong Ji</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Belani, Chandra P" sort="Belani, Chandra P" uniqKey="Belani C" first="Chandra P" last="Belani">Chandra P. Belani</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Medicine; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Yang, Jin Ming" sort="Yang, Jin Ming" uniqKey="Yang J" first="Jin-Ming" last="Yang">Jin-Ming Yang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author><author><name sortKey="Ren, Xingcong" sort="Ren, Xingcong" uniqKey="Ren X" first="Xingcong" last="Ren">Xingcong Ren</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Pharmacology; Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey</wicri:cityArea></affiliation></author></analytic><series><title level="j">Cancer biology & therapy</title><idno type="eISSN">1555-8576</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anaplastic Lymphoma Kinase</term><term>Animals</term><term>Antineoplastic Agents (pharmacology)</term><term>Autophagy (drug effects)</term><term>Cell Line, Tumor</term><term>Chloroquine (pharmacology)</term><term>Crizotinib</term><term>Down-Regulation</term><term>Drug Resistance, Neoplasm (drug effects)</term><term>Female</term><term>Heterografts</term><term>Humans</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (pathology)</term><term>Mice, Nude</term><term>Pyrazoles (pharmacology)</term><term>Pyridines (pharmacology)</term><term>Receptor Protein-Tyrosine Kinases (genetics)</term><term>Receptor Protein-Tyrosine Kinases (metabolism)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antinéoplasiques (pharmacologie)</term><term>Autophagie ()</term><term>Chloroquine (pharmacologie)</term><term>Femelle</term><term>Humains</term><term>Hétérogreffes</term><term>Lignée cellulaire tumorale</term><term>Pyrazoles (pharmacologie)</term><term>Pyridines (pharmacologie)</term><term>Récepteurs à activité tyrosine kinase (génétique)</term><term>Récepteurs à activité tyrosine kinase (métabolisme)</term><term>Régulation négative</term><term>Résistance aux médicaments antinéoplasiques ()</term><term>Souris nude</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptor Protein-Tyrosine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor Protein-Tyrosine Kinases</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Chloroquine</term><term>Pyrazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Anaplastic Lymphoma Kinase</term><term>Crizotinib</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Drug Resistance, Neoplasm</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Récepteurs à activité tyrosine kinase</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Récepteurs à activité tyrosine kinase</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Chloroquine</term><term>Pyrazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Down-Regulation</term><term>Female</term><term>Heterografts</term><term>Humans</term><term>Mice, Nude</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Autophagie</term><term>Femelle</term><term>Humains</term><term>Hétérogreffes</term><term>Lignée cellulaire tumorale</term><term>Régulation négative</term><term>Résistance aux médicaments antinéoplasiques</term><term>Souris nude</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer. Nevertheless, acquired resistance to this drug occurs inevitably in approximately a year, limiting the therapeutic benefits of this novel targeted therapy. In this study, we found that autophagy was induced in crizonitib-resistant lung cancer cells and contributed to drug resistance. We observed that ALK was downregulated in the crizotinib-resistant lung cancer cell line, H3122CR-1, and this was causally associated with autophagy induction. The degree of crizotinib resistance correlated with autophagic activity. Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway. Furthermore, we demonstrated that chloroquine, an inhibitor of autophagy, could restore sensitivity of H3122CR-1 to crizotinib and enhance its efficacy against drug-resistant lung cancer. Thus, modulating autophagy may be worth exploring as a new strategy to overcome acquired crizonitib resistance in ALK-positive lung cancer. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Pennsylvanie</li></region></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Ji, Cheng" sort="Ji, Cheng" uniqKey="Ji C" first="Cheng" last="Ji">Cheng Ji</name></noRegion></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Zhang, Li" sort="Zhang, Li" uniqKey="Zhang L" first="Li" last="Zhang">Li Zhang</name></region><name sortKey="Belani, Chandra P" sort="Belani, Chandra P" uniqKey="Belani C" first="Chandra P" last="Belani">Chandra P. Belani</name><name sortKey="Cheng, Yan" sort="Cheng, Yan" uniqKey="Cheng Y" first="Yan" last="Cheng">Yan Cheng</name><name sortKey="Ji, Shundong" sort="Ji, Shundong" uniqKey="Ji S" first="Shundong" last="Ji">Shundong Ji</name><name sortKey="Patel, Raj" sort="Patel, Raj" uniqKey="Patel R" first="Raj" last="Patel">Raj Patel</name><name sortKey="Ren, Xingcong" sort="Ren, Xingcong" uniqKey="Ren X" first="Xingcong" last="Ren">Xingcong Ren</name><name sortKey="Wang, Mian" sort="Wang, Mian" uniqKey="Wang M" first="Mian" last="Wang">Mian Wang</name><name sortKey="Wu, Hao" sort="Wu, Hao" uniqKey="Wu H" first="Hao" last="Wu">Hao Wu</name><name sortKey="Yang, Jin Ming" sort="Yang, Jin Ming" uniqKey="Yang J" first="Jin-Ming" last="Yang">Jin-Ming Yang</name><name sortKey="Zhang, Yi" sort="Zhang, Yi" uniqKey="Zhang Y" first="Yi" last="Zhang">Yi Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:24556908" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |