TGF-β in correlation with tumor progression, immunosuppression and targeted therapy in colorectal cancer

Colorectal cancer (CRC) is a complex malignancy responsible for the second-highest cancer deaths worldwide. TGF-β maintains normal cellular homeostasis by inhibiting the cell cycle and inducing apoptosis, but its elevated level is correlated with colorectal cancer progression, as TGF-β is a master regulator of the epithelial-to-mesenchymal transition, a critical step of metastasis. Tumors, including CRC, use elevated TGF-β levels to avoid immune surveillance by modulating immune cell differentiation, proliferation, and effector function. Presently, the treatment of advanced CRC is mainly based on chemotherapy, with multiple adverse effects. Thus, there is a need to develop alternate tactics because CRC continue to be mostly resistant to the present therapeutic regimen. TGF-β blockade has emerged as a promising therapeutic target in cancer therapy. Blocking TGF-β with phytochemicals and other molecules, such as antisense oligonucleotides, monoclonal antibodies, and bifunctional traps, alone or in combination, may be a safer and more effective way to treat CRC. Furthermore, combination immunotherapy comprising TGF-β blockers and immune checkpoint inhibitors is gaining popularity because both molecules work synergistically to suppress the immune system. Here, we summarize the current understanding of TGF-β as a therapeutic target for managing CRC and its context-dependent tumor-promoting or tumor-suppressing nature.