RAS Inhibitors: Changing the Paradigm from the Undruggable
Federica Campana1, Emanuela De Bellis2, Floriana Porcaro3
1Department of Human, Philosophical and Formation Sciences, University of Salerno, 84084 Fisciano, Italy.
Pharmaceutics
|July 28, 2026
Summary
RAS mutations were historically challenging drug targets. Recent KRAS G12C inhibitors like sotorasib and adagrasib have advanced RAS inhibitor development, offering new treatment options.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- RAS mutations are common in cancer but historically undruggable.
- Previous attempts to inhibit RAS proteins pharmacologically were unsuccessful.
- The emergence of targeted therapies has shifted the paradigm.
Purpose of the Study:
- To provide an updated summary of RAS inhibitor drugs.
- To detail the mechanism of action, pharmacokinetics, and toxicity of these inhibitors.
- To review efficacy studies of novel RAS-targeted therapies.
Main Methods:
- Literature review of recent advancements in RAS inhibitor development.
- Analysis of published data on drug efficacy, pharmacokinetics, and safety.
- Synthesis of information on various RAS inhibitor classes and their targets.
Main Results:
- KRAS G12C inhibitors (sotorasib, adagrasib) represent a breakthrough.
- The RAS inhibitor landscape now includes diverse compounds with varied mechanisms.
- New drugs demonstrate promising efficacy in clinical studies.
Conclusions:
- Targeting RAS mutations is now a viable therapeutic strategy.
- Continued research is essential for optimizing RAS-targeted therapies.
- These inhibitors offer new hope for patients with RAS-mutated cancers.
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