{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:38:09Z","timestamp":1791315489739,"version":"4.3.1"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023479","name":"CRIS Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>RAS<\/jats:italic>\n                    \u2010mutant cancers. In this Viewpoint, we discuss different classes of RAS inhibitors, with emphasis on those that are currently tested in the clinic including allele\u2010specific 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\n                    <jats:italic>RAS<\/jats:italic>\n                    \u2010mutant cancers.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70149","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:45:43Z","timestamp":1761763543000},"page":"2991-2995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The rapidly growing landscape of\n                    <scp>RAS<\/scp>\n                    inhibitors: from selective allele blockade to broad inhibition strategies"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-456X","authenticated-orcid":false,"given":"Matthias","family":"Drosten","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer (CIC) Consejo Superior de Investigaciones Cient\u00edficas (CSIC)\u2010Universidad de Salamanca (USAL)  Salamanca Spain"},{"name":"Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer (IBMCC) CSIC\u2010USAL  Salamanca Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-2624","authenticated-orcid":false,"given":"Mariano","family":"Barbacid","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC) Instituto de Salud Carlos III  Madrid Spain"},{"name":"Tumor Biology Program Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02903-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.013"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12796"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2024.11.009"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf1730"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00221-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00866-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-25-0349"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00679-6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.02.012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2208470"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0217"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0027"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004-025-01662-4"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2512404122"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.05.020"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.722"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08283-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","unstructured":"SangB YeLF HuF PourfarjamY Cuevas\u2010NavarroA FanS et\u00a0al.Mechanisms of resistance to active state selective tri\u2010complex RAS inhibitors.2025.bioRxiv.https:\/\/doi.org\/10.1101\/2025.04.24.649345[PREPRINT]","DOI":"10.1101\/2025.04.24.649345"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-1475"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-1425"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","unstructured":"LiakiV BarrambanaS KostopoulouM LechugaCG \u00c1lvarezR BarreroR et\u00a0al.A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.2025.bioRxiv.https:\/\/doi.org\/10.1101\/2025.08.04.668325[PREPRINT]","DOI":"10.1101\/2025.08.04.668325"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.70149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:41:05Z","timestamp":1762454465000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.70149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/1878-0261.70149"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.70149","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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