The combination of multiple receptor tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor overcomes erlotinib resistance in lung cancer cell lines through c-Met inhibition

Molecular Cancer Research : MCR
Ichiro NakachiAkitoshi Ishizaka

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) show antitumor activity in a subset of non-small cell lung cancer (NSCLC) patients. However, the initial tumor response is followed by recurrence. Several studies have suggested the importance of other receptor tyrosine kinases (RTK) and downstream kinases as potential targets in the treatment of NSCLC. We used the multiple-RTK inhibitor AEE788, which inhibits EGFR, vascular endothelial growth factor receptor, and human epidermal growth factor receptor 2, with and without the downstream kinase inhibitor RAD001 (an inhibitor of mammalian target of rapamycin). AEE788 inhibited cell growth more effectively than did erlotinib in three NSCLC cell lines examined (A549, H1650, and H1975). However, in the EGFR-TKI-resistant cell line H1975 harboring T790M resistance mutation, cell growth inhibition by AEE788 was only mild, and the phosphorylation of its leading targets such as EGFR and vascular endothelial growth factor receptor 2 was not inhibited. In H1975, AEE788 induced significantly greater cell growth inhibition when combined with RAD001 than when used alone. This cooperative effect was not seen with the combination of erlotinib and RAD001. We found that c-Met...Continue Reading

References

Oct 23, 2002·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Sug Hyung LeeNam Jin Yoo
Aug 7, 2003·Current Opinion in Pharmacology·Shile Huang, Peter J Houghton
Aug 5, 2004·Journal of the National Cancer Institute·Federico CappuzzoLucio Crinò
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patrick C MaRavi Salgia
May 12, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Roy S HerbstAlan Sandler
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eunice L KwakDaniel A Haber
Sep 15, 2005·Clinical Lung Cancer·Alex A Adjei
Sep 20, 2005·Cancer Cell·Nissim Hay
Feb 3, 2006·Cancer Research·Kathryn E O'ReillyNeal Rosen
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J RielyVincent A Miller
Mar 22, 2006·The Oncologist·Paolo MaioneFortunato Ciardiello
Jun 21, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Akira InoueToshihiro Nukiwa
Jul 22, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan Sandler, Roy Herbst
Jul 22, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John V HeymachRoy Herbst
Oct 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takayuki KosakaTetsuya Mitsudomi
Nov 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D Neil HayesMatthew Meyerson
Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J RielyWilliam Pao
Jan 30, 2007·Endocrine-related Cancer·Helen E JonesRobert I Nicholson
Feb 20, 2007·Biochemical and Biophysical Research Communications·Johann RiedemannValentine M Macaulay
Feb 24, 2007·Nature Reviews. Cancer·Sreenath V SharmaDaniel A Haber
Jul 13, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Hermien HartogWinette T A van der Graaf
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Emer O Hanrahan, John V Heymach
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bruce E JohnsonPasi A Jänne
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·James BeanWilliam Pao
Jan 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ailan GuoMichael J Comb
Aug 2, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Nicole A CiprianiRavi Salgia
Sep 2, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Hiromasa YamamotoTetsuya Mitsudomi
Oct 2, 2008·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Ichiro KawadaAkitoshi Ishizaka
Feb 26, 2009·Journal of Carcinogenesis·Neelu Puri, Ravi Salgia
Jul 4, 2009·The Lancet Oncology·Michalis V KaramouzisAthanasios G Papavassiliou

❮ Previous
Next ❯

Citations

Oct 11, 2011·Cancer Chemotherapy and Pharmacology·David A ReardonCharles Conrad
May 8, 2013·International Journal of Cancer. Journal International Du Cancer·Feifei LiLili Wang
May 28, 2014·Biochemical Pharmacology·Claudia FumarolaRoberta R Alfieri
Apr 27, 2012·Journal of Proteome Research·Tiannan GuoSiu Kwan Sze
Jun 29, 2011·Anti-cancer Drugs·Patrick Chi-pan Lau, Anthony Tak-cheung Chan
Dec 18, 2010·Oncotarget·Zhenfeng ZhangBalazs Halmos
Mar 29, 2013·Molecular Cancer Research : MCR·Hideki TeraiTomoko Betsuyaku

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.