Drug resistance in lung cancer

Manish Shanker, David Willcutts, Jack A Roth, Rajagopal Ramesh

Department of Thoracic and Cardiovascular Surgery, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA

Abstract: Resistance to chemotherapy drugs is a major problem in cancer treatment. Scientific advances made in the last two decades have resulted in the identification of genes and molecular signaling mechanisms that contribute to drug resistance. This has resulted in a better understanding of the biology of cancer cells and the way these cells adapt or undergo subtle molecular changes thereby protecting themselves from the cytotoxic effects of the anticancer drugs. Based on the knowledge gained to-date new molecularly targeted drugs are being developed and tested in clinical studies, in an attempt to overcome drug resistance and improve drug efficacy. Despite these attempts the overall 5-year survival of patients diagnosed with cancer, such as lung cancer, remains dismal and is less than 15%. It is evident that additional mechanisms contributing to drug resistance exist which are yet to be discovered. It is hoped that identification of new targets and understanding their contribution to drug resistance will provide opportunities for innovative therapies in overcoming drug resistance. In an attempt to broaden our knowledge and understanding on drug resistance we have, in this review article, summarized the most common mechanisms associated with drug resistance in lung cancer.

Keywords: lung cancer, chemotherapy, resistance, apoptosis, proteasome, DNA damage