ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- How to find a needle in a haystack: a systematic review on targeting KRAS wild-type pancreatic cancer.Future oncology (London, England) · 2024Pooled it
- Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma.Journal for immunotherapy of cancer · 2023Trial
- Targeted Therapy in Pancreatic Ductal Adenocarcinoma: Current Advances and Challenges.Current oncology (Toronto, Ont.) · 2026Review
- Pancreatic Cancer: Translating Tumor Biology into Actionability.Cancer discovery · 2026Review
- Genomic Alterations and Their Clinical Implications in Pancreatic Ductal Adenocarcinoma in a Large-Scale Chinese Cohort.Cancer medicine · 2026Article
- Brain metastasis from KRAS wild-type pancreatic cancer and organoid correlates: a case report.Journal of gastrointestinal oncology · 2026Article
- Dual pancreatic carcinomas: clonally related or independent primaries?NPJ precision oncology · 2026Article
- KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Emerging precision therapeutics for pancreatic ductal adenocarcinoma: KRAS and beyond.Therapeutic advances in medical oncology · 2026Review
- Endoscopic ultrasound molecular evaluation of pancreatic cancer trial to profile molecular landscape of inoperable pancreatic ductal adenocarcinoma.Endoscopy international open · 2026Article
- Genome-based classification of pancreatic acinar cell carcinoma reveals similarities to KRAS wild-type PDAC.Journal of translational medicine · 2025Article
- Molecular characterization and prognostic implications of KRAS mutations in pancreatic cancer patients: insights from multi-cohort analysis.NPJ precision oncology · 2025Article
- Clinicopathological and molecular characterization of KRAS wild-type pancreatic ductal adenocarcinomas reveals precursor lesions with oncogenic mutations and fusions in RAS pathway genes.The Journal of pathology · 2025Article
- Early-onset enriches the identification of actionable alterations in patients withESMO gastrointestinal oncology · 2025Article
- Molecular Subtyping and Genomic Profiling Expand Precision Medicine in KRAS Wild-Type Pancreatic Cancer.Cancer science · 2025Article
- Identification of Candidate Alterations Mediating KRASG12C Inhibitor Resistance in Advanced Colorectal and Pancreatic Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.Nature medicine · 2025Article
- Genetics and biology of pancreatic ductal adenocarcinoma.Genes & development · 2025Review
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32 authors.
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Abstract
purposeApproximately 8% to 10% of pancreatic ductal adenocarcinomas (PDAC) do not harbor mutations in KRAS. Understanding the unique molecular and clinical features of this subset of pancreatic cancer is important to guide patient stratification for clinical trials of molecularly targeted agents. EXPERIMENTAL
designWe analyzed a single-institution cohort of 795 exocrine pancreatic cancer cases (including 785 PDAC cases) with a targeted multigene sequencing panel and identified 73 patients (9.2%) with KRAS wild-type (WT) pancreatic cancer.
resultsOverall, 43.8% (32/73) of KRAS WT cases had evidence of an alternative driver of the MAPK pathway, including BRAF mutations and in-frame deletions and receptor tyrosine kinase fusions. Conversely, 56.2% of cases did not harbor a clear MAPK driver alteration, but 29.3% of these MAPK-negative KRAS WT cases (12/41) demonstrated activating alterations in other oncogenic drivers, such as GNAS, MYC, PIK3CA, and CTNNB1. We demonstrate potent efficacy of pan-RAF and MEK inhibition in patient-derived organoid models carrying BRAF in-frame deletions. Moreover, we demonstrate durable clinical benefit of targeted therapy in a patient harboring a KRAS WT tumor with a ROS1 fusion. Clinically, patients with KRAS WT tumors were significantly younger in age of onset (median age: 62.6 vs. 65.7 years; P = 0.037). SMAD4 mutations were associated with a particularly poor prognosis in KRAS WT cases.
conclusionsThis study defines the genomic underpinnings of KRAS WT pancreatic cancer and highlights potential therapeutic avenues for future investigation in molecularly directed clinical trials. See related commentary by Kato et al., p. 4527.
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