The rapidly growing landscape of RAS inhibitors: from selective allele blockade to broad inhibition strategies
Year: 2025
Type: article
Abstract: RAS oncoproteins have been considered undruggable for decades. However, recent advances have led to the development of a large variety of RAS inhibitors. While a multitude of drugs is currently under clinical evaluation, some of them have already been approved in specific contexts, leading to a continuous improvement of available therapeutic options for patients with RAS-mutant cancers. In this Viewpoint, we discuss different classes of RAS inhibitors, with emphasis on those that are currently tested in the clinic including allele-specific KRAS, panKRAS, and panRAS inhibitors. We also address determinants of response to RAS inhibition such as the tumor context or potential resistance mechanisms. Finally, we provide an outlook on the future of RAS targeting, which is likely to involve combination therapies. The rapid approval of several RAS inhibitors reflects the urgency to develop novel therapeutic strategies to treat RAS-mutant cancers.
Source: Molecular Oncology
Authors: Matthias Drosten, Mariano Barbacid
Institutions: Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Salud Carlos III, Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Spanish National Cancer Research Centre
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,300
OpenAlex ID: W4415673450