Apoptosis block as a barrier to effective therapy in non small cell lung cancer

Abstract

Lung cancer, is the most common cause of cancer death in men and second only to breast cancer in women. Currently, the first line therapy of choice is platinum-based combination chemotherapy. A therapeutic plateau has been reached with the prognosis for patients with advanced non-small cell lung cancer (NSCLC) remaining poor. New biomarkers of prognosis as well as new therapies focusing on molecular targets are emerging helping to identify patients who are likely to benefit from therapy. Despite this, drug resistance remains the major cause for treatment failure. In this article we review the role of apoptosis in mediating drug resistance in NSCLC. Better understanding of this fundamental biological process may provide a rationale for overcoming the current therapeutic plateau.

Keywords: Apoptosis, Lung cancer, Adjuvant therapy, Mitochondria, BAX, BAK, BCL2

Core tip: A therapeutic plateau has been reached with the treatment of non-small cell lung cancers with platinum-based combination chemotherapy. New biomarkers of prognosis as well as new therapies focusing on molecular targets are emerging helping to identify patients who are likely to benefit from therapy. These are as yet only available to the minority of patients. Drug resistance remains the major cause for treatment failure. Apoptosis block as a mechanism for drug resistance and potential routes to overcome this will be reviewed.