Targeting the Ccl2/Ccr2 Axis in Colorectal Cancer: Immunopharmacological Perspectives and Therapeutic Strategies Publisher Pubmed



Hajibabaie F ; Abedpoor N ; Maleki B ; Boshtam M ; Shenavar N ; Zarrabi A ; Babakhani M ; Sharifi M ; Shariati L ; Rahimmanesh I ; Cordani M
Source: Critical Reviews in Oncology/Hematology Published:2026

Abstract

Colorectal cancer, a significant contributor to cancer-related fatalities worldwide, develops due to the complex interaction between tumor cells and their immediate environment. CCL2, a type of chemokine, plays a significant role in colorectal cancer advancement through its impact on immune cell recruitment, inflammation, and metastasis. The receptor CCR2 mediates CCL2's function in directing the migration of tumor-associated macrophages (TAMs), which in turn promotes epithelial-mesenchymal transition (EMT), angiogenesis, and immune evasion. According to this narrative review, the CCL2/CCR2 axis plays a key role in both the tumor microenvironment and the metastasis of CRC. The study investigates the therapeutic possibilities of CCL2 targeting, alongside creative bioengineering methods such as siRNA and miRNA therapies, aptamers, small molecules, and CRISPR technologies. Thanks to recent developments in bioinformatics and molecular therapies, it's now possible to explore innovative strategies to block the CCL2/CCR2 pathway, potentially leading to better alternatives for treating colorectal cancer. The main focus of future studies should be on addressing therapeutic resistance, enhancing combination therapies, and identifying predictive biomarkers to enhance treatment efficacy and patient results. The study reveals complex molecular interactions regulated by CCL2, thus offering a foundation for innovative therapeutic approaches to colorectal cancer. © 2025 The Authors.