Signal pathways and precision therapy of small-cell lung cancer

Small-cell lung cancer (SCLC) encounters up 15% of all lung cancers, and is characterized by a high rate of proliferation, a tendency for early metastasis and generally poor prognosis. Most of the patients present with distant metastatic disease at the time of clinical diagnosis, and only one-third are eligible for potentially curative treatment. Recently, investigations into the genomic make-up of SCLC show extensive chromosomal rearrangements, high mutational burden and loss-of-function mutations of several tumor suppressor genes. Although the clinical development of new treatments for SCLC has been limited in recent years, a better understanding of oncogenic driver alterations has found potential novel targets that might be suitable for therapeutic approaches. Currently, there are six types of potential treatable signaling pathways in SCLC, including signaling pathways targeting the cell cycle and DNA repair, tumor development, cell metabolism, epigenetic regulation, tumor immunity and angiogenesis. At this point, however, there is still a lack of understanding of their role in SCLC tumor biology and the promotion of cancer growth. Importantly optimizing drug targets, improving drug pharmacology, and identifying potential biomarkers are the main focus and further efforts are required to recognize patients who benefit most from novel therapies in development. This review will focus on the current learning on the signaling pathways, the status of immunotherapy, and targeted therapy in SCLC.