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RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.

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Cancer immunology research 📖 저널 OA 47.1% 2024: 2/4 OA 2025: 10/22 OA 2026: 20/42 OA 2024~2026 2026 Vol.14(1) p. 90-106 OA
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유사 논문
P · Population 대상 환자/모집단
환자: NRAS-mutant melanoma treated with daraxonrasib in an ongoing phase I/Ib clinical trial
I · Intervention 중재 / 시술
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C · Comparison 대조 / 비교
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O · Outcome 결과 / 결론
Consistent with these preclinical data, objective clinical responses were observed in two patients with NRAS-mutant melanoma treated with daraxonrasib in an ongoing phase I/Ib clinical trial. Together, these data support the continued clinical evaluation of RAS(ON) multiselective inhibitors for the treatment of NRAS-mutant melanoma.

Anastacio Da Costa Carvalho L, Tovbis Shifrin N, Phadke MS, Emmons MF, Pechuan-Jorge X, Mbuga F, Ospina OE, Chow C, Seu L, Rose OL, Hegde A, Khushalani NI, Quintana E, Smalley KSM

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Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need.

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APA Anastacio Da Costa Carvalho L, Tovbis Shifrin N, et al. (2026). RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.. Cancer immunology research, 14(1), 90-106. https://doi.org/10.1158/2326-6066.CIR-25-0744
MLA Anastacio Da Costa Carvalho L, et al.. "RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.." Cancer immunology research, vol. 14, no. 1, 2026, pp. 90-106.
PMID 41186497 ↗

Abstract

Targeted therapies for NRAS-mutant melanoma remain an unmet clinical need. In this study, we demonstrate that RMC-7977, a preclinical RAS(ON) multiselective 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 MHC and PD-L1 proteins, and enhanced infiltration of CD4+ and CD8+ T cells. Complete responses were dependent on adaptive immunity, as both CD4+ and CD8+ 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 patients with NRAS-mutant melanoma treated with daraxonrasib in an ongoing phase I/Ib clinical trial. Together, these data support the continued clinical evaluation of RAS(ON) multiselective inhibitors for the treatment of NRAS-mutant melanoma.

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