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Updated: Jan 4, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Published on: July 17, 2019

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Therapeutic targeting of RAS: New hope for drugging the "undruggable"

Imran Khan1, J Matthew Rhett1, John P O'Bryan1

  • 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, United States of America; Ralph H. Johnson VA Medical Center, Charleston, SC 29401, United States of America.

Biochimica Et Biophysica Acta. Molecular Cell Research
|November 4, 2019
PubMed

Insights

Targeting RAS, a key cancer driver, has been difficult. Recent KRAS(G12C) inhibitors show promise, but broader strategies like understanding allosteric regulation are needed for effective cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS proteins are frequently mutated oncogenes driving cancer.
  • Targeting RAS has been a long-standing challenge in cancer research.
  • Recent success includes direct inhibitors for KRAS(G12C) mutations.

Purpose of the Study:

  • To review RAS biology, biochemistry, and allosteric regulation.
  • To summarize current approaches for developing RAS inhibitors.
  • To explore new avenues for targeting RAS-driven cancers.

Main Methods:

  • Literature review of RAS biology and inhibitor development.
  • Analysis of allosteric regulation mechanisms in RAS.
  • Synthesis of diverse strategies for RAS-targeted therapies.

Main Results:

  • RAS is a critical oncogene with a history of being "undruggable".
  • Specific KRAS(G12C) inhibitors represent a breakthrough.
  • Broader RAS inhibition strategies are necessary due to limited applicability of current drugs.

Conclusions:

  • Understanding RAS allosteric regulation is key to developing new inhibitors.
  • Further research is needed to overcome challenges in RAS-targeted cancer therapy.
  • Developing broadly efficacious RAS inhibitors remains a critical goal.
Keywords:
CancerDrug discoveryGTPaseMonobodyRAS inhibitorSignal transduction

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