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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Riedl, JM; Matsubara, H; McNeil, R; Patel, PS; Fece, de, la, Cruz, F; Gulhan, DC; Corcoran, RB.
Emerging landscape of KRAS inhibitors in cancer treatment.
Cancer Cell. 2026;
Doi: 10.1016/j.ccell.2026.01.001
PubMed
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- Authors Med Uni Graz:
- Riedl Jakob
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- Abstract:
- Alterations in KRAS, NRAS, and HRAS occur in roughly 20% of patients with cancer, making RAS one of the most intensively studied oncogenic targets. The discovery of mutant-selective KRASG12C inhibitors has provided a proof-of-concept for RAS-directed therapies, heralding a new era in the treatment of RAS-driven cancers. Yet, the efficacy of first-generation KRASG12C inhibitors is limited by the rapid emergence of resistance. Novel classes of (K)RAS inhibitors with distinct mechanisms of action and broader target coverage hold promise to overcome resistance and extend the benefits of RAS-targeted therapies to a wider patient population. In this review, we summarize clinical evidence for KRASG12C inhibitors across tumor types and delineate key mechanisms of resistance. We further discuss the rapidly evolving landscape of next-generation (K)RAS inhibitors, with particular emphasis on their target selectivity, mechanisms of action, preliminary clinical efficacy, and the therapeutic opportunities and challenges inherent to each class.