ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mutant KRAS is a druggable target for pancreatic cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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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
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 287 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- A Phase II Trial of an Extended-Release siRNA Implant Targeting KRASG12D/V in Locally Advanced Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients.Oncotarget · 2015Trial
- Identification and validation of natural product-based KRASMolecular diversity · 2026Article
- From Oncolysis to Adaptive Immunity: Yellow Fever Virus 17D and Ruxolitinib Activate Antitumor Immune Responses in Pancreatic Cancer Models.Biomedicines · 2026Article
- Targeting lncRNAs to Overcome Cancer Therapy Resistance: Advances in RNA Therapeutics and Delivery Strategies.Cancers · 2026Review
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Emerging Therapeutic Approaches to Pancreatic Adenocarcinoma: Advances and Future Directions.Current treatment options in oncology · 2025Review
- Evolution of direct RAS inhibitors: from undruggable target to clinical breakthroughs.Molecular cancer · 2025Review
- Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems.Pharmaceutics · 2024Review
- Consensus, debate, and prospective on pancreatic cancer treatments.Journal of hematology & oncology · 2024Review
- Sarcomatoid carcinoma of the pancreas (Review).Oncology letters · 2024Review
- Advancements in clinical RNA therapeutics: Present developments and prospective outlooks.Cell reports. Medicine · 2024Review
- KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance.Current oncology (Toronto, Ont.) · 2024Review
- Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.Current issues in molecular biology · 2024Review
- Designing cytochrome P450 enzymes for use in cancer gene therapy.Frontiers in bioengineering and biotechnology · 2024Review
- Nucleic Acid-Based Approaches to Tackle KRAS Mutant Cancers.International journal of molecular sciences · 2023Review
81 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
25 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.
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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.