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Published on: September 30, 2016
Emerging RAS-directed therapies for cancer
Michael Conroy1,2, Darren Cowzer1,2, Walter Kolch3,4
1Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
Abstract:
RAS oncogenes are the most commonly mutated oncogenes in human cancer, and RAS-mutant cancers represent a major burden of human disease. Though these oncogenes were discovered decades ago, recent years have seen major advances in understanding of their structure and function, including the therapeutic and prognostic significance of diverse isoforms. Targeting of these mutations has proven difficult, despite some successes with inhibition of RAS effector signalling. More recently, direct RAS inhibition has been achieved in a trial setting. While this has yet to be translated to everyday clinical practice, this development carries much promise. This review summarizes the diverse approaches that have been taken to RAS inhibition and then focuses on the most recent developments in direct inhibition of KRAS(G12C).
Insights
RAS oncogenes drive many cancers, but targeting them is challenging. Recent direct inhibition of KRAS(G12C) mutations shows promise for future cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- RAS oncogenes are frequently mutated in human cancers, posing a significant disease burden.
- Despite decades of research, effective targeting of RAS mutations has been difficult.
- Advances in understanding RAS isoforms and effector signaling have informed therapeutic strategies.
Purpose of the Study:
- To review diverse historical and current approaches to RAS oncogene inhibition.
- To focus on recent advancements in the direct inhibition of KRAS(G12C) mutations.
- To highlight the therapeutic potential of novel RAS-targeting strategies.
Main Methods:
- Literature review of RAS oncogene research and therapeutic strategies.
- Analysis of recent clinical trial data for direct RAS inhibitors.
- Focus on the structural and functional understanding of KRAS(G12C).
Main Results:
- Inhibition of RAS effector signaling has shown some success.
- Direct RAS inhibition has been achieved in a trial setting.
- KRAS(G12C) is a key target for direct inhibition strategies.
Conclusions:
- Direct RAS inhibition, particularly of KRAS(G12C), represents a promising new frontier in cancer therapy.
- While not yet in widespread clinical practice, these developments offer significant hope for treating RAS-mutant cancers.
- Continued research into RAS inhibition is crucial for advancing cancer treatment.
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