Targeting the Notch signaling pathway and the Notch ligand, DLL3, in small cell lung cancer

Small cell lung cancer (SCLC) is a highly aggressive and poorly differentiated cancer with high-grade neuro-endocrine (NE) features, accounting for approximately 15 % of all lung cancers. For decades, chemotherapy and radiotherapy have predominated the treatment strategy for SCLC, but relapses ensue quickly and result in poor survival of patients. Immunotherapy has brought novel insights, yet the efficacy is still restricted to a limited population with SCLC. Notch signaling is identified to play a key role in the initiation and development of SCLC, and the Notch ligand, Delta-like ligand 3 (DLL3) is found broadly and specifically expressed in SCLC cells. Thus, Notch signaling is under active exploration as a potential therapeutic target in SCLC. Herein, we summarized and updated the functional relevance of Notch signaling in SCLC, discussed Notch signaling-targeted therapy for SCLC and the correspondent preclinical and clinical trials, and investigated the promising synergy effects of Notch signaling targeted therapy and immune checkpoint inhibitors (ICIs) treatment.

Automated summary

Small cell lung cancer (SCLC) is a highly aggressive and poorly differentiated cancer with limited treatment options. Notch signaling, specifically the Notch ligand DLL3, has been identified as a potential therapeutic target in SCLC. This article summarizes the functional relevance of Notch signaling in SCLC, discusses targeted therapy and ongoing clinical trials, and explores the potential synergy with immune checkpoint inhibitors (ICIs).