Systemic Therapy For Stage Iv Small Cell Lung Cancer

Background Small cell lung cancer (SCLC) represents about 15% of all lung cancers and is characterized by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis. Less than a third of the patients have earlier stage disease at initial diagnosis, so they can receive a potentially curative multimodal therapy. Results Extensive chromosomal rearrangements and high mutation burden, almost always associated with functional inactivation of the tumour suppressor genes TP53 and RB1, were found in genomic profiling of SCLCs. Different subtypes of disease based on the relative expression of dominant transcriptional regulators revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. A better understanding of tumour biology has led to the identification of potential targets. Further strategies to direct targeted therapies to those patients who are most likely to respond are needed. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is highly promising. A small subgroup of patients shows a prolonged benefit under treatment with immunotherapy and should be explored closer. The objective must be to extend this durable benefit of effective antitumour immunity to a larger patient collective.