From Marc Ladanyi and colleagues: Lung cancer and acquired resistance to molecular therapy

http://www.ncbi.nlm.nih.gov/pubmed/21775534

Clin Cancer Res. 2011 Jul 20. [Epub ahead of print]
New Strategies in Overcoming Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer.
Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, Miller VA, Pao W.
Source
Medical Oncology, Dana-Farber Cancer Institute.

Abstract
The management of non-small cell lung cancer (NSCLC) has been transformed by the observation that lung adenocarcinomas harboring mutations in EGFR are uniquely sensitive to EGFR tyrosine kinase inhibitors (TKIs). In these patients, acquired resistance to EGFR-TKI develops after a median of 10-14 months, at which time the current standard practice is to switch to conventional cytotoxic chemotherapy. Several possible mechanisms for acquired resistance have been identified, the most common being the development of an EGFR T790M gate-keeper mutation in over 50% of cases. In this review, we discuss recent advances in the understanding of acquired TKI resistance in EGFR-mutant lung cancer and review therapeutic progress with second generation TKIs and combinations of targeted therapies.