RAS Inhibitors: Changing the Paradigm from the Undruggable

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• RAS mutations are historically difficult targets in cancer drug development.
• Previous attempts to inhibit RAS mutations pharmacologically were unsuccessful.
• The emergence of KRAS G12C inhibitors marks a significant breakthrough.

Purpose of the Study:

• To provide an updated summary of RAS inhibitor drugs.
• To detail the mechanisms of action, pharmacokinetics, and toxicity of RAS inhibitors.
• To review efficacy studies of current RAS inhibitor therapies.

Main Methods:

• Literature review of RAS inhibitor drugs.
• Analysis of mechanisms of action.
• Summary of pharmacokinetic and toxicity data.
• Compilation of efficacy study results.

Main Results:

• The development of KRAS G12C inhibitors (sotorasib, adagrasib) has transformed the field.
• The landscape of RAS inhibitors now includes multiple compounds with diverse mechanisms.
• Updated data on pharmacokinetics, toxicity, and efficacy are crucial for clinical application.

Conclusions:

• RAS inhibitors represent a rapidly evolving area in cancer therapy.
• Newer agents offer targeted approaches for specific RAS mutations.
• This review synthesizes current knowledge on RAS inhibitors for researchers and clinicians.