Targeting non-histone methylation in gastrointestinal cancers: From biology to clinic

Gastrointestinal (GI) cancers, encompassing a range of malignancies within the digestive tract, present significant challenges in both diagnosis and treatment, reflecting a dire need for innovative therapeutic strategies. This article delves into the profound influence of non-histone methylation on the pathogenesis and evolution of gastrointestinal (GI) cancers. Non-histone proteins, undergoing methylation by enzymes such as Protein Arginine Methyltransferases (PRMTs) and Lysine Methyltransferases (KMTs), play pivotal roles in cellular signaling, metabolism, chromatin remodeling, and other processes crucial for cancer development. This review illuminates the complex mechanisms by which non-histone methylation affects key aspects of tumor biology, including oncogenesis, growth, proliferation, invasion, migration, metabolic reprogramming, and immune escape in GI malignancies. Highlighting recent discoveries, this work underscores the importance of non-histone methylation in cancer biology and its potential as a target for innovative therapeutic strategies aimed at improving outcomes for patients with GI cancers.