Effect of Dasatinib on EMT-mediated-mechanism of Resistance Against EGFR Inhibitors in Lung Cancer Cells

作者: Yuichi Sesumi , Kenichi Suda , Hiroshi Mizuuchi , Yoshihisa Kobayashi , Katsuaki Sato

DOI: 10.1016/J.LUNGCAN.2016.12.012

关键词:

摘要: Abstract Objective The epithelial to mesenchymal transition (EMT) is associated with acquired resistance epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies overcome or prevent EMT are needed. A recent report suggested dasatinib (an ABL/Src inhibitor) inhibits induced by transforming (TGF)-beta (Wilson et al., 2014). In this study, we analyzed effects of on the mechanism HCC4006 cells, which tend acquire EGFR-TKIs EMT. Materials and methods Sensitivity erlotinib-resistant (ER) an phenotype was analyzed. against combination erlotinib (HCC4006EDR) following chronic these drugs. expression markers were Results Short-term long-term did not reverse HCC4006ER. contrast, HCC4006EDR maintained phenotype, underlying plus therapy attributable a T790M secondary mutation. but HCC4006ER highly sensitive third-generation EGFR-TKI, osimertinib. Conclusions Although monotherapy preemptive prevented emergence led T790M. Our results indicate may be promising strategy EMT-mediated resistance.

参考文章(46)
Wen-Lei Zhuo, Yan Wang, Xian-Lu Zhuo, Yun-Song Zhang, Zheng-Tang Chen, Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway. Biochemical and Biophysical Research Communications. ,vol. 369, pp. 1098- 1102 ,(2008) , 10.1016/J.BBRC.2008.02.143
L. V. Sequist, B. A. Waltman, D. Dias-Santagata, S. Digumarthy, A. B. Turke, P. Fidias, K. Bergethon, A. T. Shaw, S. Gettinger, A. K. Cosper, S. Akhavanfard, R. S. Heist, J. Temel, J. G. Christensen, J. C. Wain, T. J. Lynch, K. Vernovsky, E. J. Mark, M. Lanuti, A. J. Iafrate, M. Mino-Kenudson, J. A. Engelman, Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors Science Translational Medicine. ,vol. 3, ,(2011) , 10.1126/SCITRANSLMED.3002003
Alexa B. Turke, Kreshnik Zejnullahu, Yi-Long Wu, Youngchul Song, Dora Dias-Santagata, Eugene Lifshits, Luca Toschi, Andrew Rogers, Tony Mok, Lecia Sequist, Neal I. Lindeman, Carly Murphy, Sara Akhavanfard, Beow Y. Yeap, Yun Xiao, Marzia Capelletti, A. John Iafrate, Charles Lee, James G. Christensen, Jeffrey A. Engelman, Pasi A. Jänne, Preexistence and Clonal Selection of MET Amplification in EGFR Mutant NSCLC Cancer Cell. ,vol. 17, pp. 77- 88 ,(2010) , 10.1016/J.CCR.2009.11.022
Kenichi Suda, Hiroshi Mizuuchi, Yoshihiko Maehara, Tetsuya Mitsudomi, Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation—diversity, ductility, and destiny Cancer and Metastasis Reviews. ,vol. 31, pp. 807- 814 ,(2012) , 10.1007/S10555-012-9391-7
D. Ross Camidge, William Pao, Lecia V. Sequist, Acquired resistance to TKIs in solid tumours: learning from lung cancer Nature Reviews Clinical Oncology. ,vol. 11, pp. 473- 481 ,(2014) , 10.1038/NRCLINONC.2014.104
Satoshi Watanabe, Takashi Sone, Tomoharu Matsui, Kenta Yamamura, Mayuko Tani, Akihito Okazaki, Koji Kurokawa, Yuichi Tambo, Hazuki Takato, Noriyuki Ohkura, Yuko Waseda, Nobuyuki Katayama, Kazuo Kasahara, Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma Lung Cancer. ,vol. 82, pp. 370- 372 ,(2013) , 10.1016/J.LUNGCAN.2013.06.003
J. A. Engelman, K. Zejnullahu, T. Mitsudomi, Y. Song, C. Hyland, J. O. Park, N. Lindeman, C.-M. Gale, X. Zhao, J. Christensen, T. Kosaka, A. J. Holmes, A. M. Rogers, F. Cappuzzo, T. Mok, C. Lee, B. E. Johnson, L. C. Cantley, P. A. Janne, MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling Science. ,vol. 316, pp. 1039- 1043 ,(2007) , 10.1126/SCIENCE.1141478
Vincent Fallet, Anne-Marie Ruppert, Virginie Poulot, Roger Lacave, Laure Belmont, Martine Antoine, Jacques Cadranel, Marie Wislez, Armelle Lavolé, Secondary Resistance to Erlotinib: Acquired T790M Mutation and Small-Cell Lung Cancer Transformation in the Same Patient Journal of Thoracic Oncology. ,vol. 7, pp. 1061- 1063 ,(2012) , 10.1097/JTO.0B013E31824FEA45
Kenichi Suda, Kenji Tomizawa, Makiko Fujii, Hideki Murakami, Hirotaka Osada, Yoshihiko Maehara, Yasushi Yatabe, Yoshitaka Sekido, Tetsuya Mitsudomi, Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib. Journal of Thoracic Oncology. ,vol. 6, pp. 1152- 1161 ,(2011) , 10.1097/JTO.0B013E318216EE52
Kenichi Suda, Kenji Tomizawa, Tetsuya Mitsudomi, Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer and Metastasis Reviews. ,vol. 29, pp. 49- 60 ,(2010) , 10.1007/S10555-010-9209-4