ReviewCancer biology & medicine2025
Drugging the 'undruggable' KRAS: breakthroughs, challenges, and opportunities in pancreatic cancer.
Review in Cancer biology & medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- 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
- RAS Inhibitors: Changing the Paradigm from the Undruggable.Pharmaceutics · 2026Review
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Gut microbiota and pancreatic cancer: tumorigenesis, progression, and clinical applications.Cancer biology & medicine · 2026Review
- KRAS inhibition is an effective therapy for appendiceal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Deciphering RTK-RAS and MAPK Pathway Dependencies in Gemcitabine-Treated Pancreatic Ductal Adenocarcinoma Through Conversational Artificial Intelligence.International journal of molecular sciences · 2026Article
- Conversational Artificial Intelligence Agents-Enabled Dissection of RTK-RAS and MAPK Pathway Dependencies in Gemcitabine-Treated Pancreatic Ductal Adenocarcinoma (PDAC).medRxiv : the preprint server for health sciences · 2026Article
- Emerging Therapeutic Landscapes for KRAS-Mutant Pancreatic Ductal Adenocarcinoma: Beyond the "Undruggable" Paradigm.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Review
- Knowledge Discovery and Drug-Repurposing Framework for Pancreatic Ductal Adenocarcinoma: Molecular Networking and Computational Docking.Computational and structural biotechnology journal · 2026Article
- Bracing for the storm: emerging resistance mechanisms to KRAS inhibitors in pancreatic cancer and strategies to overcome them.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy.Cells · 2025Review
- Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions.Oncology research · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis that is driven primarily by oncogenic KRAS mutations present in > 90% of cases. KRAS mutations, particularly the G12D mutation which dominates in PDAC, fuel tumor initiation, progression, and immune evasion, thereby contributing to therapy resistance. Nevertheless, KRAS has long been considered "undruggable" due to its structure. Recent advances have spurred transformative progress in direct KRAS inhibition. While FDA-approved mutation-specific and pan-KRAS inhibitors show limited efficacy in PDAC, emerging agents (MRTX1133 and RMC-9805) have demonstrated preclinical promise. However, resistance remains a critical hurdle and is driven by pathway reactivation, secondary mutations, and metabolic adaptations. Alternative strategies targeting upstream regulators (SHP2 and SOS1) aim to block KRAS activation and associated resistance mechanisms. Preclinical studies have also highlighted synergistic benefits of combining KRAS inhibitors with MEK, PI3K, or CDK4/6 inhibitors, which are now undergoing clinical evaluation. Immunotherapies, including KRAS-targeted vaccines and adoptive T-cell therapies, have further expanded the therapeutic landscape of enhancing KRAS-targeted therapies in PDAC. The molecular basis of KRAS-driven PDAC, current inhibitors, resistance mechanisms, and innovative strategies are discussed herein to address treatment barriers. Opportunities to improve clinical outcomes are underscored in this challenging malignancy by integrating insights from preclinical and clinical research.
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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.