Cancer-associated fibroblasts of colorectal cancer: Translational prospects in liquid biopsy and targeted therapy

Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts (CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component of the tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectal carcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patient survival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinical applications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected in blood samples, have been proposed to help in determining patient prognosis and enables the detection of cancer through liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, and shows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensively to be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have been reported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumor cell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization of CAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRC patient management in the future.