ArticleProceedings of the National Academy of Sciences of the United States of America2020
Unbiased in vivo preclinical evaluation of anticancer drugs identifies effective therapy for the treatment of pancreatic adenocarcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- A tri-scale in silico framework integrating pharmacovigilance and mechanistic modeling suggests tepotinib-associated acute kidney injury risk.Renal failure · 2026Article
- Niclosamide nanoparticles enhance pancreatic cancer sensitivity to gemcitabine via HIF-1α inhibition.iScience · 2025Article
- Heat Shock Proteins in Pancreatic Cancer: Pathogenic Mechanisms and Clinical Implications.Cells · 2025Review
- Inhibition of interferon regulatory factor 4 orchestrates T cell dysfunction, extending mouse cardiac allograft survival.Chinese medical journal · 2025Article
- MYC Overexpression Enhances Sensitivity to MEK Inhibition in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2025Article
- The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.Gastroenterology · 2024Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- High CD142 Level Marks Tumor-Promoting Fibroblasts with Targeting Potential in Colorectal Cancer.International journal of molecular sciences · 2023Article
- USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities.Cell reports. Medicine · 2023Article
- A Self-Assembling Peptide as a Model for Detection of Colorectal Cancer.Gels (Basel, Switzerland) · 2022Article
- The pivotal application of patient-derived organoid biobanks for personalized treatment of gastrointestinal cancers.Biomarker research · 2022Review
- Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.Communications biology · 2021Article
- Modeling pancreatic cancer in mice for experimental therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2021Review
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 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, which limits surgical options and portends a dismal prognosis. Current oncologic PDAC therapies confer marginal benefit and, thus, a significant unmet clinical need exists for new therapeutic strategies. To identify effective PDAC therapies, we leveraged a syngeneic orthotopic PDAC transplant mouse model to perform a large-scale, in vivo screen of 16 single-agent and 41 two-drug targeted therapy combinations in mice. Among 57 drug conditions screened, combined inhibition of heat shock protein (Hsp)-90 and MEK was found to produce robust suppression of tumor growth, leading to an 80% increase in the survival of PDAC-bearing mice with no significant toxicity. Mechanistically, we observed that single-agent MEK inhibition led to compensatory activation of resistance pathways, including components of the PI3K/AKT/mTOR signaling axis, which was overcome with the addition of HSP90 inhibition. The combination of HSP90(i) + MEK(i) was also active in vitro in established human PDAC cell lines and in vivo in patient-derived organoid PDAC transplant models. These findings encourage the clinical development of HSP90(i) + MEK(i) combination therapy and highlight the power of clinically relevant in vivo model systems for identifying cancer therapies.
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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.