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Updated: May 5, 2026

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

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The very druggable RAS proteins

Marie C Hasselluhn1, Kenneth P Olive1

  • 1Department of Medicine, Division of Digestive and Liver Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.

Trends in Cancer
|October 30, 2025
PubMed

Insights

Targeting RAS proteins, mutated in many cancers, is now possible with new inhibitors. Recent research highlights EFTX-G12V and MCB-36 as precision therapies for RAS-driven cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS genes are crucial for cell growth and survival.
  • Oncogenic mutations in RAS genes drive numerous human cancers.
  • Targeting RAS proteins was historically challenging, with them being considered 'undruggable'.

Purpose of the Study:

  • To review recent advances in developing targeted therapies for RAS-driven cancers.
  • To highlight innovative inhibitors challenging the 'undruggable' RAS.
  • To showcase precision strategies for RAS-targeted therapies.

Main Methods:

  • Review of recent scientific literature on RAS-targeted therapies.
  • Identification and description of novel therapeutic agents.
  • Analysis of allele-specific and pan-RAS targeting strategies.

Main Results:

  • EFTX-G12V, an EGFR-directed allele-specific RNAi therapeutic, has been developed.
  • MCB-36, a dual-state pan-KRAS degrader, represents a new therapeutic approach.
  • These agents exemplify advancements in precision medicine for RAS-related cancers.

Conclusions:

  • Innovative inhibitors are effectively challenging historically 'undruggable' RAS.
  • Precision RAS-targeted strategies, including RNAi therapeutics and degraders, show significant promise.
  • Recent advances pave the way for more effective treatments for patients with RAS-driven cancers.
Keywords:
RAS allele-specific therapyRAS selectivityprecision oncologytumor specificity

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