The changing therapeutic landscape of small-cell lung cancer

Small-cell lung cancer (SCLC) is an exceptionally aggressive malignancy: highly proliferative, heterogeneous, and frequently metastatic at diagnosis. Although initially responsive to chemotherapy, such responses are typically transient, and recurrent disease has been largely refractory to standard cytotoxics. The past decade has been notable for major advances in our understanding of SCLC biology, and this preclinical progress is now informing multiple novel therapeutic approaches for this disease. Of particular note, defining cell-surface proteins that are uniquely or differentially expressed in SCLC has led to various targeted therapies showing substantial preliminary evidence of efficacy in patients with SCLC. Approaches in active development include T-cell engagers, antibody-drug conjugates, radioconjugates, and cell therapies, among others. In this Series paper, we summarise current standards of care, recent advances, and highlight emerging approaches showing early promise for better management of SCLC. Together, these advances are providing new hope for patients with what has been a particularly lethal disease.