Cancer-associated fibroblasts as key mediators of therapeutic resistance and tumor progression in colorectal cancer

Abstract

Cancer-associated fibroblasts (CAFs) are instrumental in tumor progression by interacting with tumor cells, other stromal components, and the extracellular matrix (ECM) within the tumor stroma. The origin, heterogeneity, and activation mechanisms of CAFs in different cancer types have been widely reported. Their roles and mechanisms of therapeutic resistance in colorectal cancer (CRC) have only recently been explored. This review presents the most relevant evidence on CAF biology in CRC, including their subtypes, markers, role in ECM remodeling, and roles in signaling pathways associated with therapeutic failure and tumor progression. We further consider the contribution of CAFs to therapeutic resistance, highlighting potential agents from preclinical studies and clinical trials targeting CAFs in CRC. Based on the most recent findings, we consider the potential of targeting CAFs as a strategy to disrupt the tumor-supportive microenvironment and improve therapeutic efficacy. The review highlights key advances in the field that may contribute to improving the survival of patients with CRC and similar cancers, particularly those showing resistance to classic therapies such as chemotherapy and radiotherapy.