Mechanistic insights into SUMOylation and its role in cancer pathogenesis: bridging oncogenesis, immunity, and therapeutic opportunities.

SUMOylation is a post-translational modification mediated by SUMO proteins, a family of small ubiquitin-like biological macromolecules that covalently attach to specific lysine residues in target proteins. This modification regulates various macromolecular functions, including transcriptional control, subcellular localization, DNA repair, and cell cycle progression. Recent advances have unveiled the multifaceted roles of SUMOylation in cancer pathogenesis, encompassing oncogenesis, immune modulation, and therapeutic resistance. This review details the molecular mechanisms of SUMOylation and its deregulation in tumor development, highlighting its role in genomic stability, transcriptional regulation, and signal transduction, key elements in tumor progression and metastasis. Additionally, the role of SUMOylation in the tumor microenvironment (TME) and immune evasion is explored, with emphasis on its interactions with immune checkpoint pathways and inflammatory signaling. Insights into SUMOylation's involvement in treatment resistance, particularly chemoresistance and radioresistance, are presented alongside an overview of emerging therapeutic strategies targeting this pathway. The potential of SUMOylation as a diagnostic and prognostic biomarker is also discussed, underscoring its translational significance in personalized oncology. By bridging oncogenesis, immune regulation, and therapy, this review aims to unify the current understanding of SUMOylation's role in cancer. Targeting SUMOylation presents a promising avenue for developing innovative cancer therapies that address immune modulation and treatment resistance. This review provides a roadmap for future research, fostering advancements in SUMOylation biology and its therapeutic applications in oncology.