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Updated: Oct 5, 2025

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Unraveling and targeting RAS-driven metabolic signaling for therapeutic gain

Jonathan M DeLiberty1, Ryan Robb1, Claire E Gates1

  • 1Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Advances in Cancer Research
|February 1, 2022
PubMed

Insights

RAS mutations drive many deadly cancers by altering cell metabolism. Targeting these metabolic changes, including upregulated glycolysis and nutrient scavenging, offers new therapeutic strategies for RAS-mutant cancers.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • RAS mutations are frequent oncogenic drivers in human cancers, leading to limited treatment options and high mortality rates.
  • Aberrant RAS signaling significantly alters cancer cell metabolism, a known hallmark of cancer.
  • RAS-driven cancers exhibit specific metabolic alterations, including increased glycolysis, altered nutrient scavenging (autophagy, macropinocytosis), and modified glutamine metabolism.

Purpose of the Study:

  • To review the unique metabolic requirements induced by aberrant RAS signaling in cancer.
  • To identify how these altered metabolic dependencies can be therapeutically exploited.

Main Methods:

  • Literature review of studies on RAS mutations and cancer metabolism.
  • Analysis of metabolic pathways upregulated in RAS-driven cancers.
  • Examination of therapeutic strategies targeting metabolic vulnerabilities.

Main Results:

  • RAS-driven cancers display a distinct metabolic profile characterized by upregulated glycolysis and nutrient scavenging.
  • These metabolic alterations are crucial for tumorigenesis, proliferation, and survival in nutrient-poor conditions.
  • The unique metabolic landscape also confers resistance to standard cancer therapies.

Conclusions:

  • Aberrant RAS signaling creates specific metabolic dependencies in cancer cells.
  • Targeting these metabolic vulnerabilities, particularly with metabolic inhibitors, presents a promising therapeutic avenue.
  • Metabolic inhibitors are currently in clinical trials for RAS-mutant cancers, highlighting their therapeutic potential.
Keywords:
AutophagyGlycolysisMacropinocytosisMetabolismMitochondriaRASScavenging

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