82IN - Molecular mechanisms of acquired resistance to kinase inhibitors

Date 01 October 2012
Event ESMO Congress 2012
Session Latest innovations in NSCLC management
Topics Pathology/Molecular Biology
Non-small-cell lung cancer
Basic Scientific Principles
Presenter Lecia Sequist
Authors L.V. Sequist
  • Center For Thoracic Cancers, Massachusetts General Hospital, 02114 - Boston/US


The discovery of mutations in the epidermal growth factor receptor (EGFR) gene was been a turning point in clinical lung cancer care. We now know from multiple phase 3 randomized clinical trials that patients with advanced lung cancer should be screened for EGFR mutations at the time of diagnosis and that first-line genotype-specific therapy with EGFR tyrosine kinase inhibitors (TKIs) can improve progression-free survival and quality of life compared to standard chemotherapy. In the last few years we have seen other examples of successful genotype-directed therapy for lung cancers with ALK and ROS translocations. However, one significant obstacle that we face in the clinic today is the development of acquired resistance to therapy. In this lecture, we will review what is known about acquired resistance to TKI therapies and discuss possible strategies for treating and/or preventing acquired resistance.


L.V. Sequist: I have done paid consulting for Clovis Oncology and GSK. I have done pro-bono consulting for Merrimack Pharmaceuticals, Boehringer-Ingelheim and Daiichi-Sankyo