From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer

Trophoblast cell surface antigen 2 (TROP2) is a type I transmembrane glycoprotein that was initially identified in studies related to trophoblastic cells and has been implicated in epithelial cell proliferation and the maintenance of cellular stemness. While TROP2 is expressed at low levels in normal epithelial tissues, it is markedly overexpressed in a wide range of malignancies, including small cell lung cancer (SCLC), where it plays a critical role in promoting tumor cell proliferation, invasion, and metastasis. SCLC is characterized by aggressive biological behavior, early dissemination, and rapid development of therapeutic resistance. Despite improvements in first-line outcomes achieved with the combination of immunotherapy and chemotherapy, patients with relapsed or refractory disease continue to face low response rates, high recurrence, and substantial treatment-related toxicity. With antibody-drug conjugates (ADCs) targeting human epidermal growth factor receptor 2 (HER2) demonstrating clear clinical benefit in HER2-mutant non-small cell lung cancer (NSCLC), the tumor-selective overexpression of TROP2 relative to normal tissues has positioned it as an attractive target for ADC-based therapy. TROP2-targeted ADCs therefore represent an innovative therapeutic strategy and offer new promise for the treatment of SCLC. In this review, we systematically summarize the biological characteristics of TROP2 and the emerging clinical evidence supporting TROP2-directed ADCs in SCLC. We further propose an application framework integrating TROP2 expression levels, SCLC molecular subtypes, and DNA damage response (DDR) status, and discuss future research directions, including deeper characterization of TROP2 biology, optimization of combination strategies with immunotherapy and DDR-targeted agents, and the development of precision treatment approaches based on standardized TROP2 assessment and relevant biomarkers.