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Small cell lung cancer (SCLC) is known to be the most aggressive of all thoracic malignancies, notoriously known for its very poor prognosis. Platinum-based chemotherapy has been the standard of care for decades. Despite years of research, no treatment novelties with significant impact on survival have been achieved until recently. The last few years have witnessed light at the end of the tunnel with immunotherapy proving to improve survival. Nevertheless, responses were not homogeneous in all subgroups, and finding who would best benefit from treatment remains unanswered. Multiple limitations exist, and the quest for optimal biomarkers seemed unfruitful until the discovery of different SCLC phenotypes. In this review, the authors briefly discuss SCLC phenotypes and biomarker assays. Then, the authors continue with the main trials of SCLC treatment using chemotherapy, immunotherapy, and targeted treatment in the frontline or subsequent line settings. Research has been extensively implemented to better understand the biology of SCLC and test for the optimal use of immunotherapy in patients with SCLC, as well as to enhance responses via possible combinations. Targeted mechanisms of action have also been attempted; yet no solid proof of efficacy has been established.

Therapeutic modalities in small cell lung cancer: a paradigm shift after decades of quiescence