Beyond the genomic mutation: Rethinking the molecular biomarkers of K-RAS dependency in pancreatic cancers

Carla Mottini, Luca Cardone

Research output: Contribution to journalReview articlepeer-review

Abstract

Oncogenic v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) plays a key role in the development and maintenance of pancreatic ductal adenocarcinoma (PDAC). The targeting of K-RAS would be beneficial to treat tumors whose growth depends on active K-RAS. The analysis of K-RAS genomic mutations is a clinical routine; however, an emerging question is whether the mutational status is able to identify tumors effectively dependent on K-RAS for tailoring targeted therapies. With the emergence of novel K-RAS inhibitors in clinical settings, this question is relevant. Several studies support the notion that the K-RAS mutation is not a sufficient biomarker deciphering the effective dependency of the tumor. Transcriptomic and metabolomic profiles of tumors, while revealing K-RAS signaling complexity and K-RAS-driven molecular pathways crucial for PDAC growth, are opening the opportunity to specifically identify K-RAS-dependent-or K-RAS-independent tumor subtypes by using novel molecular biomarkers. This would help tumor selection aimed at tailoring therapies against K-RAS. In this review, we will present studies about how the K-RAS mutation can also be interpreted in a state of K-RAS dependency, for which it is possible to identify specific K-RAS-driven molecular biomarkers in certain PDAC subtypes, beyond the genomic K-RAS mutational status.

Original languageEnglish
Article number5023
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number14
DOIs
Publication statusPublished - Jul 2 2020

Keywords

  • Biomarkers
  • Genomic mutations
  • K-RAS oncogene
  • Metabolomics
  • Oncogene dependency
  • Pancreatic cancer
  • Targeted therapies
  • Transcriptomics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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