A recent review highlights that post-translational modifications add a dynamic regulatory layer to KRAS beyond canonical GDP/GTP cycling, controlling membrane localization and trafficking, nucleotide exchange, effector engagement, protein stability, and degradation. Targeting PTM enzymes and modification-dependent regulatory networks may provide new therapeutic opportunities and strategies to overcome resistance in KRAS-driven cancers.
KRAS-driven cancer is a highly complex and dynamically regulated disease in which oncogenic signaling extends beyond genetic mutations to multiple layers of post-translational control. In a recent review published in Advanced Cancer Research , the authors provide an overview of RAS post-translational modifications, highlighting their important roles in regulating protein localization, stability, activity, and signaling output.
By modulating membrane trafficking, nucleotide cycling, effector interactions, and protein degradation, post-translational modifications add a critical regulatory layer to the canonical GDP/GTP switch of RAS. This work systematically summarizes the major types and functional consequences of RAS modifications and further discusses emerging therapeutic strategies targeting PTM-related enzymes and regulatory networks, offering new opportunities for the treatment of KRAS-driven cancers.
Key highlights include:
Citation: Yao N, Yang L, Zhou R, Wang J, Li X. Post-translational modifications of KRAS: from molecular regulation to therapeutic targeting. Adv. Cancer Res. 2026(3):0014, https://doi.org/10.55092/acr20260014.
Advanced Cancer Research
Literature review
Cells
Post-translational modifications of KRAS: from molecular regulation to therapeutic targeting
24-Sep-2026