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Updated: Oct 5, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Targeting the "undruggable" RAS with biologics

Michael Whaby1, Imran Khan2, John P O'Bryan2

  • 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.

Advances in Cancer Research
|February 1, 2022
PubMed

Insights

Developing anti-RAS biologics offers new therapeutic strategies for human cancers driven by RAS proteins. This review explores novel biologics targeting various RAS mutations beyond KRASG12C.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS proteins are key drivers in human cancer development.
  • Targeting RAS is a major focus for cancer therapy.
  • Existing therapies primarily target KRASG12C, leaving other mutations unaddressed.

Purpose of the Study:

  • To review the emerging field of anti-RAS biologics.
  • To highlight novel therapeutic vulnerabilities in oncogenic RAS.
  • To discuss the potential of biologics in developing new anti-RAS therapies.

Main Methods:

  • Literature review of anti-RAS biologic research.
  • Analysis of current and emerging anti-RAS therapeutic strategies.
  • Discussion of preclinical and clinical developments in anti-RAS biologics.

Main Results:

  • Several anti-RAS biologics have been developed.
  • These biologics reveal new vulnerabilities in oncogenic RAS.
  • Progress has been made in targeting specific RAS mutations.

Conclusions:

  • Anti-RAS biologics represent a promising new avenue for cancer treatment.
  • Further development is needed to target a broader range of RAS mutations.
  • Biologics hold potential for novel anti-RAS therapies.
Keywords:
AntibodiesCyclic peptidesDARPinsIntrabodiesMiniproteinsMonobodiesPROTACsSso7dStapled peptidesToxin peptidasescancer therapeutics

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