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Targeted Therapy in Lung Cancer: Lessons Learned from Past Experiences

Exactly a 100 years ago, the discovery of a cancer-causing virus by Rous1 laid the foundations for research on the molecular basis of cancer. Initially, this finding was met with considerable skepticism; however, subsequent work on Rous sarcoma virus led to the discovery of the first known cancerassociated molecular alteration, the proto-oncogene c-src.2,3 Since then, we have come a long way in our understanding of the molecular alterations that drive cancer. Identifying and targeting the key driver molecular alterations has led to the development of some remarkably effective therapies against cancer. The development of imatinib for the treatment of chronic myelogenous leukemia and trastuzumab for breast cancer opened a new era in the treatment of cancer. In the past decade, a number of clinical trials with molecularly targeted drugs in the treatment of lung cancer and particularly in non-small cell lung cancer (NSCLC). However, only a few of the targeted therapies have shown promise in the treatment of lung cancer. In the 11th annual meeting of molecularly targeted therapy in NSCLC, a number of molecularly targeted drugs were discussed. Given the large number of targeted therapies under evaluation, it is important to reflect on our past experience with targeted therapies and identify lessons that are relevant for effective drug development in future. On the basis of our review of the past successes and failures with targeted therapy in cancer, we have identified the following key points that would be of relevance to future drug development in lung cancer.