Targeted therapies for small cell lung cancer: where do we stand?

Lung cancer is the leading cause of cancer-related mortality and is subdivided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC accounts for around 15% of all cases of lung cancer and is associated with cigarette smoking and an extremely dismal prognosis. Standard therapeutic regimens involving chemotherapy and radiotherapy have been improved over the past decades, but without a major impact on long term patient survival. In view of the potentially limited impact of the further developments of standard therapeutic regimens on patient survival, the development of targeted therapies based on a better understanding of the molecular basis of the disease is urgently needed. At the genetic level, SCLC appears to be very heterogenous, although somatic mutations targeting classical oncogenes and tumor suppressors, such as MYC, TP53 and RB1 have been reported. In addition, SCLC possesses somatic mutations in many other cancer genes, including transcription factors, enzymes involved in chromatin modification, receptor tyrosine kinases and their downstream signaling components. Several avenues have been explored to develop targeted therapies for SCLC, including receptor tyrosine kinase signaling, angiogenesis, Ras, the PI3 K/Akt/mTOR (PAM) pathway, the Hedgehog pathway, the apoptotic machinery, epigenetics and immunotherapy. So far, however, there has been limited success with these targeted approaches in clinical trials. Further progress in the optimization of targeted therapies for SCLC will require the development of more personalized approaches for the patients. It is hoped that recent progress in whole genome sequencing will facilitate the selection of targeted therapies tailored to the genetic background of individual SCLC patients.

http://www.sciencedirect.com/science/article/pii/S1040842815000475

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