Protein succinylation in tumors-from biology to clinical therapy

Lysine succinylation is a recently identified post-translational modification (PTM) characterized by the transfer of a succinyl group (-CO-CH2-CH2-CO2H) to lysine residues, primarily mediated by succinyl-CoA. This modification plays a critical role in maintaining protein stability and function, and is involved in diverse biological processes, including energy metabolism, substrate transport, and signal transduction. Accumulating evidence indicates that lysine succinylation contributes to tumorigenesis and cancer progression, with both enzymatic and non-enzymatic mechanisms playing regulatory roles. This review summarizes recent advances in succinylation research within the context of tumor metabolism, the tumor immune microenvironment, and its interplay with other epigenetic modifications. Furthermore, we highlight current developments in anti-tumor therapeutics and succinylation inhibitors, aiming to provide novel insights into protein post-translational modifications and to support the identification of potential drug targets for clinical applications.