Despite its intriguing findings, the present study still has some limitations: (1) we have not explored the reason behind the downregulation of SDHC in CRC; (2) Further research is needed to understand the mechanism by which SDHC deficiency improves PI3K/AKT phosphorylation; (3) The potential drug inducing synthetic lethality in SDHC-deficient colorectal cancer cells requires further investigation. Here, SDHC is linked to colorectal cancer.