Current understanding of free fatty acids and their receptors in colorectal cancer treatment.

• Free fatty acid receptors are involved in colorectal cancer pathophysiology. • Free fatty acid receptor ligands are considered promising antitumor agents. • Polyunsaturated fatty acids have proven anticancer properties. • Butyrate can support conventional therapy against colorectal cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Currently, dietary factors are being emphasized in the pathogenesis of CRC. There is strong evidence that fatty acids (FAs) and free FA receptors (FFARs) are involved in CRC. This comprehensive review discusses the role of FAs and their receptors in CRC pathophysiology, development, and treatment. In particular, butyrate and n-3 polyunsaturated fatty acids have been found to exert anticancer properties by, among others, inhibiting proliferation and metastasis and inducing apoptosis in tumor cells. Consequently, they are used in conjunction with conventional therapies. Furthermore, FFAR gene expression is down-regulated in CRC, suggesting their suppressive character. Recent studies showed that the FFAR4 agonist, GW9508, can inhibit tumor growth. In conclusion, natural as well as synthetic FFAR ligands are considered promising candidates for CRC therapy. Schematic representation of the role of fatty acids on CRC development. Dietary fat components, mainly SCFAs (such as butyrate) and PUFAs, influence the risk of CRC through several mechanisms, such as inhibition of cell proliferation, maintenance of intestinal barrier, immune system modulation, epigenetic modification, and induction of apoptosis and autophagy. It is proven that free fatty acid receptors are involved in these mechanisms. Abbreviations: CRC, colorectal cancer; FFAR, free fatty acid receptor; HDACs, histone deacetylases; LCFAs, long chain fatty acids; PUFAs, polyunsaturated fatty acids; SCFAs, short chain fatty acids. [Display omitted] [ABSTRACT FROM AUTHOR]