ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
A Small Molecule with Big Impact: MRTX1133 Targets the KRASG12D Mutation in Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 118 citations in OpenAlex.
- Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.JCO precision oncology · 2025Trial
- Targeting adaptive EGFR feedback enhances the therapeutic efficacy of RMC-6236 in cholangiocarcinoma.Experimental hematology & oncology · 2026Article
- Review
- High-Sensitivity ctDNA Analysis Uncovers Relevant Signals Missed by NGS in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Review
- KRAS and TP53 Circulating Tumor DNA are Prognostic in Localized Pancreatic Cancer.Annals of surgical oncology · 2026Article
- KRAS-Targeted Therapies in NSCLC: Resistance, Combination Strategies, and Emerging Clinical Paradigms.Medical oncology (Northwood, London, England) · 2026Review
- Synthetic lethality targets in pancreatic ductal adenocarcinoma: prevalence and limitations of liquid biopsy detection in a minority-serving cancer center.Future oncology (London, England) · 2026Article
- Bergamottin demonstrates preclinical effectiveness against pancreatic cancer by modulating PPAR-γ to induce apoptosis.Translational cancer research · 2026Article
- Targeted Therapy in Pancreatic Ductal Adenocarcinoma: Current Advances and Challenges.Current oncology (Toronto, Ont.) · 2026Review
- Versatile Palladium-Catalyzed C-H Arylation of Fluoroarenes with 2-Chloropyridine Derivatives.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Precision Therapeutics in Pancreatic Cancer: Emerging Targeted, Immune, and Antibody-Drug Conjugate Strategies Exemplified by Adagrasib, Dostarlimab, and Trastuzumab Deruxtecan.Journal of clinical medicine · 2026Review
- KRAS inhibition is an effective therapy for appendiceal adenocarcinoma.Journal of hematology & oncology · 2026Article
- Rosindol: A fluorogen for the quantitative measurement of reactive oxygen species in living cells.bioRxiv : the preprint server for biology · 2026Article
- KRAS (G12D)-selective inhibitor MRTX1133 suppresses proliferation and differentially modulates chemosensitivity in ovarian mucinous carcinoma.Oncology letters · 2026Article
- Dehydrocorydaline Exerts Anti-Pancreatic Cancer Effects Through the PI3K/Akt/mTOR Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Single-nucleotide variant profiling in liquid biopsy with RECO-Cas.Science advances · 2026Article
- Gel-Based NMR Method for Observing Submicrosecond Protein Dynamics at Atomic Resolution.The journal of physical chemistry letters · 2026Article
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- Preclinical Characterization and Clinical Activity of RNK08954, a Highly Selective and Orally Bioavailable KRASG12D Inhibitor.Cancer discovery · 2026Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
KRAS mutations drive oncogenic alterations in numerous cancers, particularly in human pancreatic ductal adenocarcinoma (PDAC). About 93% of PDACs have KRAS mutations, with G12D (∼42% of cases) and G12V (∼32% of cases) being the most common. The recent approval of sotorasib (AMG510), a small-molecule, covalent, and selective KRASG12C inhibitor, for treating patients with non-small cell lung cancer represents a breakthrough in KRAS targeted therapy. However, there is a need to develop other much-needed KRAS-mutant inhibitors for PDAC therapy. Notably, Mirati Therapeutics recently developed MRTX1133, a small-molecule, noncovalent, and selective KRASG12D inhibitor through extensive structure-based drug design. MRTX1133 has demonstrated potent in vitro and in vivo antitumor efficacy against KRASG12D-mutant cancer cells, especially in PDAC, leading to its recent initiation of a phase I/II clinical trial. Here, we provide a summary of the recent advancements related to the use of MRTX1133 for treating KRASG12D-mutant PDAC, focusing on its efficacy and underlying mechanistic actions. In addition, we discuss potential challenges and future directions for MRTX1133 therapy for PDAC, including overcoming intrinsic and acquired drug resistance, developing effective combination therapies, and improving MRTX1133's oral bioavailability and target spectrum. The promising results obtained from preclinical studies suggest that MRTX1133 could revolutionize the treatment of PDAC, bringing about a paradigm shift in its management.
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Registered trials
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.