Proteomic Perspectives on KRAS-Driven Cancers and Emerging Therapeutic Approaches

Authors

Ramesh Karki
Ru Chen
Sheng Pan

Language

English

Publication Date

11-2-2025

Journal

Current Oncology

DOI

41294676

PMID

PMC12650995

PMCID

PMC12650995

PubMedCentral® Posted Date

11-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS interactome, aberrant signaling pathways and dysregulated cellular processes contributing to tumorigenesis. This review discusses current knowledge on proteomic alterations associated with oncogenic KRAS mutations, with particular focus on allele-specific proteome signatures and the roles of post-translational modifications (PTMs) of KRAS in modulating the functional networks. Furthermore, we highlight recent therapeutic advances targeting KRAS variants and discuss emerging resistance mechanisms from a proteomics-informed perspective.

Keywords

Humans, Proteomics, Proto-Oncogene Proteins p21(ras), Neoplasms, Mutation, Molecular Targeted Therapy, KRAS, cancer, proteomics, interactome, post-translational modifications (PTMs), KRAS inhibition

Published Open-Access

yes

Recommended Citation

Ramesh Karki, Ru Chen, and Sheng Pan, "Proteomic Perspectives on KRAS-Driven Cancers and Emerging Therapeutic Approaches" (2025). Faculty, Staff and Student Publications. 6391.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6391