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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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The importance of Ras in drug resistance in cancer

Fiona M Healy1, Ian A Prior2, David J MacEwan1

  • 1Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology (ISMIB), University of Liverpool, Liverpool, UK.

British Journal of Pharmacology
|February 26, 2021
PubMed

Insights

Oncogenic Ras mutations drive cancer drug resistance. New allele-specific therapies offer hope for targeting this previously undruggable protein, improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Ras proteins are crucial in cellular proliferation and survival pathways.
  • Mutations in Ras are linked to cancer initiation, drug resistance, and relapse.
  • Directly targeting Ras has been challenging due to its structure and function, making it 'undruggable'.

Purpose of the Study:

  • To review the role of oncogenic Ras mutations in cancer drug resistance.
  • To discuss progress in overcoming Ras-mediated resistance through pharmacological targeting.
  • To highlight emerging therapeutic strategies for Ras-driven cancers.

Main Methods:

  • Literature review analyzing the impact of Ras mutations on drug resistance.
  • Examination of pharmacological approaches to abrogate Ras-mediated resistance.
  • Discussion of recent advancements in Ras-targeting drug development.

Main Results:

  • Ras mutations are a significant factor in cancer therapeutic resistance.
  • Despite challenges, novel drug classes and analytical techniques are emerging.
  • Direct, allele-specific Ras inhibitors have entered clinical trials.

Conclusions:

  • Targeting Ras remains a critical challenge in cancer therapy.
  • Advances in drug development offer new hope for treating Ras-driven cancers.
  • Emerging direct Ras-targeting agents represent a significant breakthrough.
Keywords:
Drug resistanceMAPKPI3Kacquired resistancecancer stem cellsintrinsic resistance

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