Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity

Small cell lung cancer (SCLC) is a devastating disease with high proliferative and metastatic capacity. SCLC has been classified into molecular subtypes based on differential expression of lineage-defining transcription factors. Recent studies have proposed new subtypes that are based on both tumor-intrinsic and -extrinsic factors. SCLC demonstrates substantial intratumoral subtype heterogeneity characterized by highly plastic transcriptional states, indicating that the initially dominant subtype can shift during disease progression and in association with resistance to therapy. Strategies to promote or constrain plasticity and cell fate transitions have nominated novel targets that could prompt the development of more durably effective therapies for patients with SCLC. In this review, we describe the latest advances in SCLC subtype classification and their biological and clinical implications.