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Therapeutic strategies to target RAS-mutant cancers

Meagan B Ryan1,2, Ryan B Corcoran3,4

  • 1Massachusetts General Hospital Cancer Center, Boston, MA, USA.

Nature Reviews. Clinical Oncology
|October 3, 2018
PubMed

Insights

Targeting RAS-mutant cancers remains challenging due to difficulties in direct inhibition. This review explores historical and current strategies, including direct and indirect approaches, to overcome RAS oncogene effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS genes are frequently mutated oncogenes in various cancers.
  • Developing effective therapies against RAS-mutant cancers is a significant clinical challenge.
  • Directly inhibiting RAS proteins has historically proven difficult.

Purpose of the Study:

  • To review historical and ongoing efforts to target RAS-mutant cancers.
  • To outline the current therapeutic landscape for RAS-targeted therapies.
  • To discuss diverse strategies aimed at overcoming the effects of RAS oncogenes.

Main Methods:

  • Review of scientific literature on RAS-targeted cancer therapies.
  • Analysis of clinical trial data for emerging RAS-targeting strategies.
  • Exploration of direct and indirect therapeutic approaches.

Main Results:

  • Direct RAS inhibition strategies are progressing, with several in clinical trials.
  • Indirect targeting methods show promise, including effector inhibition and synthetic lethality.
  • Combination therapies and immunotherapy represent advanced strategies.

Conclusions:

  • Despite challenges, significant progress is being made in targeting RAS-mutant cancers.
  • A multifaceted approach combining direct, indirect, and combination strategies is crucial.
  • Continued research is vital to overcome the oncogenic effects of RAS.

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