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Direct inhibition of RAS: Quest for the Holy Grail?

Russell Spencer-Smith1, John P O'Bryan1

  • 1Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA; University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown VA Medical Center, Chicago, IL, USA.

Seminars in Cancer Biology
|December 18, 2017
PubMed

Insights

Targeting RAS GTPases, frequently mutated in cancer, is challenging due to their structure. Recent advances offer new hope for developing effective RAS inhibitors for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS GTPases (H-, K-, and N-RAS) are key regulators of cell signaling.
  • These proteins are the most frequently mutated oncoprotein family in human cancers.
  • Their unique biochemical properties have historically made them
  • undruggable
  • therapeutic targets.

Purpose of the Study:

  • To review the current landscape of RAS inhibition strategies.
  • To discuss the methodologies employed in targeting RAS.
  • To highlight the challenges in developing clinically viable RAS-targeting therapeutics.

Main Methods:

  • Literature review of recent advancements in drug screening.
  • Analysis of molecular modeling techniques for RAS.
  • Examination of studies on RAS protein function and inhibition.

Main Results:

  • Despite previous assumptions, novel approaches are emerging for RAS targeting.
  • Progress has been made in understanding RAS biology and identifying druggable pockets.
  • Several strategies are under investigation, including direct inhibitors and pathway modulators.

Conclusions:

  • Targeting RAS GTPases remains a significant challenge in oncology.
  • Recent scientific advancements have revitalized efforts to develop RAS inhibitors.
  • Overcoming therapeutic hurdles is crucial for translating these discoveries into effective cancer treatments.
Keywords:
CancerHigh-throughput screeningRAS biologicsRAS inhibitorRAS monobody

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