ArticleCancer research2023
Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis.Cell stem cell · 2026Article
- CDK8 remodels the tumor microenvironment and promotes resistance to KRASThe EMBO journal · 2026Article
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Pancreatic Cancer: Translating Tumor Biology into Actionability.Cancer discovery · 2026Review
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 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
- Overcoming Adaptive Resistance to KRASG12D Blockade in Pancreatic Cancer through Vertical Pathway Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Single-Cell Computational Frameworks for Quantifying BET Bromodomain Inhibitor Resistance and Screening Re-Sensitizer Drugs in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An AI-derived peptide PCa2 suppresses pancreatic cancer growth via modulation of the ErbB/PI3K/AKT/mTOR/MYC signaling axis.Cell communication and signaling : CCS · 2026Article
- High-throughput screening identifies NT-1 that synergizes with MRTX1133 against acquired resistant KRASNPJ precision oncology · 2026Article
- Pharmaco-genomic characterization of pancreatic and biliary tract cancer tumoroids for drug response.iScience · 2026Article
- The Combination of a BCL-xL PROTAC and an mTOR Inhibitor Sensitizes Pancreatic Ductal Adenocarcinoma to KRASCancers · 2026Article
- High prevalence ofPleura and peritoneum · 2026Article
- Dual Inhibition of KRAS G12D and PI3K/BRD4 signaling overcomes therapeutic resistance in pancreatic cancer.Acta biomaterialia · 2026Article
- Combination of PARP and KRASNature communications · 2026Article
- CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer.Cancer research · 2026Article
- HDAC5 deficiency induces intrinsic resistance to KRAS inhibition by disrupting c-Myc acetylation-ubiquitination homeostasis.The Journal of clinical investigation · 2026Article
- ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC.Nature chemical biology · 2026Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a low survival rate. Recently, new drugs that target KRASG12D, a common mutation in PDAC, have been developed. We studied one of these compounds, MRTX1133, and found it was specific and effective at low nanomolar concentrations in patient-derived organoid models and cell lines harboring KRASG12D mutations. Treatment with MRTX1133 upregulated the expression and phosphorylation of EGFR and HER2, indicating that inhibition of ERBB signaling may potentiate MRTX1133 antitumor activity. Indeed, the irreversible pan-ERBB inhibitor, afatinib, potently synergized with MRTX1133 in vitro, and cancer cells with acquired resistance to MRTX1133 in vitro remained sensitive to this combination therapy. Finally, the combination of MRTX1133 and afatinib led to tumor regression and longer survival in orthotopic PDAC mouse models. These results suggest that dual inhibition of ERBB and KRAS signaling may be synergistic and circumvent the rapid development of acquired resistance in patients with KRAS mutant pancreatic cancer. SIGNIFICANCE: KRAS-mutant pancreatic cancer models, including KRAS inhibitor-resistant models, show exquisite sensitivity to combined pan-ERBB and KRAS targeting, which provides the rationale for testing this drug combination in clinical trials.
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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.