Ras-Directed Therapies: A Revolution

Dear Colleagues,

The Ras pathway is one of the most frequently deregulated signaling pathways in cancer. In recent years, the development of a plethora of therapeutic agents that directly target Ras has opened up new avenues to target Ras-driven tumors. While the first direct Ras inhibitors developed were KRAS-G12C(OFF) inhibitors, now, over ten classes of Ras-directed therapies are being evaluated via preclinical models and clinical trials. These include agents that target specific Ras mutants; wild-type and mutant variants of a single Ras isoform; or multiple Ras isoforms, either in their GDP-bound (inactive) state, their GTP-bound (active) state, or both. Evaluating how Ras-driven tumors respond to all these different therapeutic agents in terms of downstream target inhibition and depth and duration of response, understanding differences in toxicity profiles, and elucidating common and specific mechanisms of resistance will be crucial in moving these drugs forward into the clinic.

We are pleased to invite you to contribute your valuable work to this Special Issue, “Ras-Directed Therapies: A Revolution”.

This Special Issue will collect papers focused on preclinical studies on the efficacy and mechanisms of resistance of direct Ras inhibitors and degraders in Ras-driven tumors.

For this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

• Therapeutic efficacy in preclinical models;
• Cell signaling and phenotypic changes in response to Ras-directed drugs;
• Mechanisms of resistance;
• Combination therapies based on Ras-directed drugs.

I look forward to receiving your contributions.

Dr. Naiara Perurena
Guest Editor

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