Targeted drugs in small-cell lung cancer

Abstract

In contrast to non-small-cell lung cancer (NSCLC), few advances have been made in systemic treatment of small-cell lung cancer (SCLC) in recent years. Most patients are diagnosed with extensive stage disease and are commonly treated with platinum-based chemotherapy which, although attaining high initial objective responses, has a limited impact on survival. Due to the dismal prognosis of SCLC, novel and more effective treatment strategies are urgently needed. A deeper characterization of the genomic landscape of SCLC has led to the development of rational and promising targeted agents. However, despite a large number of clinical trials, results have been disappointing and there are still no approved targeted drugs for SCLC. Recent comprehensive genomic studies suggest SCLC is a heterogeneous disease, characterized by genomic alterations targeting a broad variety of genes, including those involved in transcription regulation and chromatin modification which seem to be a hallmark of this specific lung cancer subtype. Current research efforts are focusing on further understanding of the cellular and molecular abnormalities underlying SCLC development, progression and resistance to chemotherapy. Unraveling the genomic complexity of SCLC could be the key to optimize existing treatments, including chemotherapy and radiotherapy, and for identifying those patients most likely to benefit from selected targeted therapeutic approaches.

Keywords: SOX2; Small-cell lung cancer (SCLC); retinoblastoma; targeted therapies; tumor suppressor genes.