CEACAM5-Targeted Therapies in Solid Tumors: Biological Barriers and Next-Generation Precision Strategies
Year: 2026
Type: review
Abstract: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is an attractive therapeutic target because of its widespread overexpression in epithelial malignancies and its polarised, largely luminal expression in normal epithelium. Despite extensive clinical development, no CEACAM5-targeted drug has received regulatory approval. The Phase III CARMEN-LC03 trial highlighted the limitations of expression-based patient selection, as tusamitamab ravtansine failed to improve the ORR over docetaxel in patients with high CEACAM5 expression. This review argues that progress in CEACAM5-targeted therapy requires a shift from focusing solely on target expression to understanding the target's biological constraints. We first summarize the biological functions of CEACAM5 in tumor progression, then discuss the major biological barriers limiting therapeutic efficacy including GPI anchor-mediated slow internalization, soluble CEACAM5-mediated antigen sink effects, extensive glycosylation, antigen heterogeneity, and immunosuppressive tumor microenvironment. Building on these biological barriers, we outline five priorities for next-generation development: targeting tumor-specific glycoforms, multi-antigen strategies, microenvironment remodeling, conditionally restricted delivery, and biomarker-guided clinical trial design. Future patient selection should integrate CEACAM5 expression with target biology and therapeutic modality compatibility to identify patients likely to benefit and reduce ineffective treatment.
DOI: 10.2147/dddt.s650566
Authors: Tingting Ye, Ruohan Mei, Xiaoting Liu, Panpan Huang
Institution: Gannan Medical University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,836
Award: G6419683083
OpenAlex ID: W7225176304