Targeting cellular energy metabolism- mediated ferroptosis by small molecule compounds for colorectal cancer therapy.

Alterations in cellular energy metabolism, including glycolysis, glutamine and lipid metabolism that affects ferroptosis in the tumor microenvironment (TME), play a critical role in the development and progression of colorectal cancer (CRC) and offer evolutionary advantages to tumor cells and even enhance their aggressive phenotype. This review summarizes the findings on the dysregulated energy metabolism pathways, including lipid and fatty acid metabolism especially for regulating the ferroptosis in TME. Moreover, the cellular energy metabolism and tumor ferroptosis to be regulated by small molecule compounds, which targeting the different aspects of metabolic pathways of energy production as well as metabolic enzymes that connect with the tumor cell growth and ferroptosis in CRC are also discussed. In this review, we will provide a comprehensive summary on small molecule compounds regulatory function of different energy metabolic routes on ferroptosis in tumor cells and discuss those metabolic vulnerabilities for the development of potential ferroptosis-based tumor therapies for colorectal cancer.