ArticleCancer discovery2025
T-cell Dependency of Tumor Regressions and Complete Responses with RAS(ON) Multi-selective Inhibition in Preclinical Models of Pancreatic Ductal Adenocarcinoma.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed.
- Surufatinib plus tislelizumab as later-line therapy for metastatic colorectal cancer: a single-arm, phase II trial.BMC cancer · 2026Trial
- Exosome-like nanoparticles derived fromInternational journal of pharmaceutics: X · 2026Article
- Activity and specificity of KRAS variants-directed Revolution Medicines Company (RMC) compounds for pleural effusion-derived non-small cell lung cancer cell lines.Translational lung cancer research · 2026Article
- Daraxonrasib and the era of pan-RAS inhibition: mechanisms, clinical advances, and resistance landscapes.Experimental hematology & oncology · 2026Review
- Review
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- Review
- From RAS inhibitor resistance to rational combination strategies.Nature medicine · 2026Article
- Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer.Nature communications · 2026Article
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- The basal cell state maintains pancreatic cancers by controlling an immunosuppressive circuit.bioRxiv : the preprint server for biology · 2026Article
- Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in colorectal cancer.Cancer cell · 2026Article
- Mutant KRAS peptide vaccine with dual checkpoint blockade in metastatic colorectal cancer: a phase I trial.Nature communications · 2026Article
- A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Variable efficacy of the non-covalent KRASNPJ precision oncology · 2026Article
- KRAS-driven immune exclusion in pancreatic ductal adenocarcinoma: mechanisms and therapeutic reversal.The oncologist · 2026Review
- Abrogation of Oncogenic RAS Signaling by a RAS(ON) Inhibitor Doublet Primes Immune-Refractory KRASG12C-Mutant NSCLC for Immune Checkpoint Blockade.Cancer discovery · 2026Article
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Efficacy of dual KRASCell death & disease · 2026Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Activating mutations in KRAS drive tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), promoting tumor cell proliferation and contributing to an immunosuppressive tumor microenvironment, rendering PDAC tumors insensitive to immunotherapy. RAS(ON) multi-selective inhibitors, such as daraxonrasib (RMC-6236) and RMC-7977, target the active state of RAS, with potent antitumor activity in PDAC murine models. In this study, we report that RAS(ON) multi-selective inhibition led to rapid and profound PDAC regressions in immunocompetent mice, decreasing myeloid cells and increasing T cells and macrophages in the tumor microenvironment. The depth and duration of tumor regression depended on T cells and conventional dendritic cells. Moreover, the combination of RAS(ON) multi-selective inhibitors with immunotherapy conferred deeper and more durable tumor regressions, including complete responses not seen with either treatment alone. In summary, concurrent inhibition of mutant and wild-type RAS is active in concert with T-cell immunotherapy, revealing RAS(ON) multi-selective inhibitors as a potential therapeutic immuno-sensitizing strategy in PDAC. SIGNIFICANCE: RAS(ON) multi-selective inhibitors enhance antitumor immunity in preclinical models of PDAC, resulting in deeper and more durable responses when combined with immunotherapy. These findings support the clinical evaluation of immune-based strategies that may prolong the response to RAS inhibitor therapies as well as overcome issues of therapeutic resistance to inhibitors alone. See related commentary by Lasse Opsahl and Pasca di Magliano, p. 1537.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.