Multiple resistant factors in lung cancer with primary resistance to EGFR-TK inhibitors confer poor survival

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Go Woon KimJae Cheol Lee

Abstract

EGFR activating mutations have been recognized as the most important predictor of response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, 20-30% of patients harboring EGFR activating mutations show a poor response requiring investigation for underlying mechanisms. Characteristics of 541 patients with lung cancer harboring EGFR activating mutations were analyzed to determine contributing factors that could differentiate responders and non-responders. In addition, previously suggested moleculo-pathologic factors of resistance such as IκB, IGF1R, PTEN, MET, AXL and BIM were evaluated in patients exhibiting primary resistance who had sufficient biopsied tissues available for analyses. Responders to EGFR-TKIs had a higher incidence of deletion mutations and more frequent presence of EGFR amplifications than non-responders. The median OS was 21 months (95% CI 26.1-30.4) in responders compared to 8 months (95% CI 8.7-15.8) in non-responders (p<0.001). In analyses of patients with primary resistance, we found that 27.3% (6/22) of them exhibited decreased expression of IκB, and 9.1% (2/22) of patients showed increased expression of IGF1R. Loss of PTEN was noted in 54.5%, and BIM polymorphism was found in 19% of patients. No pa...Continue Reading

References

Jun 8, 2000·Journal of the National Cancer Institute·G L MutterC Eng
Sep 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fred R HirschWilbur A Franklin
May 5, 2005·Journal of the National Cancer Institute·Federico CappuzzoMarileila Varella-Garcia
Jun 14, 2005·Cancer Cell·Yardena SamuelsVictor E Velculescu
Jul 15, 2005·The New England Journal of Medicine·Ming-Sound TsaoFrances A Shepherd
Dec 21, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S K ChanM E Hill
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J RielyVincent A Miller
Nov 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fred R HirschBrian Holloway
Feb 10, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lecia V SequistDaniel A Haber
Apr 6, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Hideki EndohTetsuya Mitsudomi
Jul 6, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daniel B CostaMark S Huberman
Sep 1, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Peter GoldstrawUNKNOWN Participating Institutions
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
Jul 4, 2008·The New England Journal of Medicine·Shyamala MaheswaranDaniel A Haber
Jul 16, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Chang-Qi ZhuUNKNOWN National Cancer Institute of Canada Clinical Trials Group Study BR.21
Aug 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jenn-Yu WuPan-Chyr Yang
Dec 20, 2008·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Ludmila PrudkinIgnacio I Wistuba
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David M JackmanBruce E Johnson
Aug 21, 2009·The New England Journal of Medicine·Rafael RosellUNKNOWN Spanish Lung Cancer Group
Dec 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David JackmanVincent A Miller
Jun 25, 2010·The New England Journal of Medicine·Makoto MaemondoUNKNOWN North-East Japan Study Group
Oct 23, 2010·Nature Reviews. Cancer·William Pao, Juliann Chmielecki
Mar 25, 2011·Science Translational Medicine·Lecia V SequistJeffrey A Engelman
Jan 31, 2012·The Lancet Oncology·Rafael RosellUNKNOWN Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia T
Jul 4, 2012·Nature Genetics·Zhenfeng ZhangTrever G Bivona
Aug 18, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Yoshihiko FujitaKazuto Nishio
Jan 19, 2013·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Su Jin LeeMyung-Ju Ahn
Sep 11, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·K NishinoA Kumanogoh
Jan 29, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Hye Ryun KimJoo Hang Kim
Apr 17, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kazutoshi IsobeSakae Homma

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Citations

Aug 14, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiaoqing ZhangZhemin Zhang
Apr 27, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Hisham SaafanChristoph A Ritter
Oct 23, 2016·Clinical Lung Cancer·Yuri SheikineDaniel B Costa
Apr 3, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Keunchil ParkSantiago Viteri

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