{"id":47445,"date":"2025-11-04T18:47:39","date_gmt":"2025-11-04T17:47:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/04\/rason-multi-selective-inhibition-drives-antitumor-immunity-in-preclinical-models-of-nras-mutant-melanoma\/"},"modified":"2025-11-04T18:47:39","modified_gmt":"2025-11-04T17:47:39","slug":"rason-multi-selective-inhibition-drives-antitumor-immunity-in-preclinical-models-of-nras-mutant-melanoma","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/04\/rason-multi-selective-inhibition-drives-antitumor-immunity-in-preclinical-models-of-nras-mutant-melanoma\/","title":{"rendered":"RAS(ON) multi-selective inhibition drives antitumor immunity in preclinical models of NRAS-mutant melanoma"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Nov 4. doi: 10.1158\/2326-6066.CIR-25-0744. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. Here, we demonstrate that RMC-7977, a preclinical RAS(ON) multi-selective inhibitor representative of the investigational agent daraxonrasib (RMC-6236), was able to elicit potent antitumor immune responses across multiple NRAS-mutant melanoma models. Treatment with RMC-7977 led to rapid tumor regressions driven by inhibition of MAPK signaling, upregulation of major histocompatibility complex (MHC) and PD-L1 proteins, and enhanced infiltration of CD4\u207a and CD8\u207a T cells. Complete responses were dependent on adaptive immunity, as both CD4\u207a and CD8\u207a T cells were essential for extended survival. Resistance to treatment was marked by reduced T-cell infiltration, loss of MHC class I expression, and expansion of myeloid-derived suppressor cells. Combining RMC-7977 with anti-PD-1 boosted cytotoxic T-cell infiltration, reprogrammed myeloid cells toward an antigen-presenting phenotype, and improved survival in models resistant to PD-1 blockade. Consistent with these preclinical data, objective clinical responses were observed in two NRAS-mutant melanoma patients treated with daraxonrasib in an ongoing Phase I\/Ib clinical trial. Together, these data support the continued clinical evaluation of RAS(ON) multi-selective inhibitors for the treatment of NRAS-mutant melanoma.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41186497\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20251104124737&amp;v=2.18.0.post22+67771e2\">41186497<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0744\">10.1158\/2326-6066.CIR-25-0744<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Nov 4. doi: 10.1158\/2326-6066.CIR-25-0744. Online ahead of print. ABSTRACT Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. Here, we demonstrate that RMC-7977, a preclinical RAS(ON) multi-selective inhibitor representative of the investigational agent daraxonrasib (RMC-6236), was able to elicit potent antitumor immune responses across multiple NRAS-mutant melanoma models. Treatment with &#8230; <a title=\"RAS(ON) multi-selective inhibition drives antitumor immunity in preclinical models of NRAS-mutant melanoma\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/11\/04\/rason-multi-selective-inhibition-drives-antitumor-immunity-in-preclinical-models-of-nras-mutant-melanoma\/\" aria-label=\"Read more about RAS(ON) multi-selective inhibition drives antitumor immunity in preclinical models of NRAS-mutant melanoma\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-47445","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/47445","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=47445"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/47445\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=47445"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=47445"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=47445"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}