2026/07/14 by Nicole M. Peña Ruiz, Martin E. Fernandez-Zapico · 1 voice
Biochemistry, Genetics and Molecular Biology · #Epigenetics and DNA Methylation #Genomics and Rare Diseases #PI3K/AKT/mTOR signaling in cancer
paper · doi:10.1172/jci208392
openalex publication_date 2026/07/14 · openalex created_date 2026/07/15 · openalex updated_date 2026/07/27
Members of the type 2 histone lysine methyltransferase family (KMT2s) are key drivers of enhancer activation and are the most mutated group of epigenetic regulators in different cancer types. Within this family, KMT2C and KMT2D have the highest mutational incidence across various cancers. To evaluate their role in gastric cancer, Wang et al. developed a Pten deficiency-driven genetically engineered mouse model with inducible loss of Kmt2c and Kmt2d in gastric epithelial cells. Through extensive in vitro, in vivo, and in silico analyses, the authors revealed that the concomitant loss of Kmt2c and Kmt2d promotes gastric carcinogenesis while enhancing antigen presentation and sensitivity to immunotherapy and targeted approaches like mTOR inhibition, highlighting the tumor-suppressive roles of KMT2C/D in gastric cancer and uncovering a vulnerability for this dismal condition.