Unraveling the genomic complexity of small-cell lung cancer

Significant clinical advances have been made in the last few years regarding lung cancer management. Molecularly targeted therapies have allowed a personalized approach for the treatment of patients with advanced non-small cell lung cancer (NSCLC). Immunotherapy has also advanced with promising results in the treatment of several tumors, including lung cancer. Immune checkpoint inhibitors are now at the forefront of immunotherapy and two antibodies against PD-1 (nivolumab and pembrolizumab) are approved for NSCLC. Despite the significant progress that has been achieved in NSCLC, such progress is rather limited in small cell lung cancer (SCLC). The treatment of SCLC patients has not significantly changed in the last 30 years and no effective targeted therapies are currently available (1). Since curative intent resections are not usually performed in SCLC, there is a paucity of tumor material for the performance of translational research. This problem has now been overcome with the development of new model systems, mainly genetically engineered mouse models (GEMMs) that give us the opportunity to understand the biology and molecular biology of SCLC. It is widely accepted that SCLC is a high-grade neuroendocrine carcinoma with several molecular and cellular abnormalities (2). Tumor suppressor genes, such as retinoblastoma 1 (RB1) and tumor protein p53 (TP53), are inactivated in the majority of patients with SCLC (2). Somatic inactivation of RB1 and TP53 (double knockout) is used to establish GEMMs as models for biological and preclinical studies of SCLC (3). In addition, a vast amount of knowledge has been gained by high throughput molecular profile technologies