ArticleCancer discovery2023
Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 260 papers.
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The trial behind it
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
260 citing papers in PubMed.
- Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial.Nature medicine · 2026Trial
- A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- Pancreatic Cancer KRAS Breakthrough: Drug Graveyard No More.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-rasGastroenterology · 2026Article
- ARNTL2 promotes metastatic phenotypes through SERPINE1 transcription in KRAS G12D pancreatic cancer.iScience · 2026Article
- Review
- Targeting KRAS reprograms a Treg-dominant immunosuppressive microenvironment and sensitizes KRAS-mutant gastric adenocarcinoma to CTLA-4 immunotherapy.Science China. Life sciences · 2026Article
- KRAS Inhibitor-Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.Cancer research · 2026Article
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- Emerging Therapeutic Strategies for Non-G12C KRAS Mutations in Colorectal Cancer: Focusing on G12D and G12V.Journal of gastrointestinal cancer · 2026Review
- Review
- Targeted KRASG12V Degradation In Vivo Elicits Lung Adenocarcinoma Regression with Subsequent Relapse from Dysregulated Proteolysis.Cancer research · 2026Article
- Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis.Developmental cell · 2026Article
- CDK8 remodels the tumor microenvironment and promotes resistance to KRASThe EMBO journal · 2026Article
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- Emerging Precision Therapeutic Strategies in Pancreatic Ductal Adenocarcinoma: KRAS Targeting, DDR Vulnerabilities, Immune Redirection, and Tumor Microenvironment Remodeling.Pharmaceutics · 2026Review
- KRASScience advances · 2026Article
- ATM Deficiency Induces TGFβ-Mediated Stromal Programming in Pancreatic Cancer.Cancer research · 2026Article
200 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors.
Funding
Abstract
Mutations in the KRAS oncogene are found in more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), with Gly-to-Asp mutations (KRASG12D) being the most common. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in implantable and autochthonous PDAC models with an intact immune system. In vitro studies validated the specificity and potency of MRTX1133. In vivo, MRTX1133 prompted deep tumor regressions in all models tested, including complete or near-complete remissions after 14 days. Concomitant with tumor cell apoptosis and proliferative arrest, drug treatment led to marked shifts in the tumor microenvironment (TME), including changes in fibroblasts, matrix, and macrophages. T cells were necessary for MRTX1133's full antitumor effect, and T-cell depletion accelerated tumor regrowth after therapy. These results validate the specificity, potency, and efficacy of MRTX1133 in immunocompetent KRASG12D-mutant PDAC models, providing a rationale for clinical testing and a platform for further investigation of combination therapies. SIGNIFICANCE: Pharmacologic inhibition of KRASG12D in pancreatic cancer models with an intact immune system stimulates specific, potent, and durable tumor regressions. In the absence of overt toxicity, these results suggest that this and similar inhibitors should be tested as potential, high-impact novel therapies for patients with PDAC. See related commentary by Redding and Grabocka, p. 260. This article is highlighted in the In This Issue feature, p. 247.
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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.