ArticleOncotarget2017
Targeting ERK enhances the cytotoxic effect of the novel PI3K and mTOR dual inhibitor VS-5584 in preclinical models of pancreatic cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Crosstalk between KRAS and miRNAs in pancreatic cancer: Opportunities for its diagnosis, prognosis and therapeutic intervention (Review).International journal of oncology · 2026Review
- ASH2L induces tamoxifen resistance via H3K4me3 dependent ITGA6/ERK signaling in ER-positive breast cancer.British journal of cancer · 2026Article
- Oncogenic KRAS triggers metabolic reprogramming in pancreatic ductal adenocarcinoma.Journal of translational internal medicine · 2023Article
- The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.NPJ precision oncology · 2023Article
- Review
- ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors.Cell reports. Medicine · 2021Article
- Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers.International journal of molecular sciences · 2020Review
- Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2020Review
- Machine Learning and Network Analyses Reveal Disease Subtypes of Pancreatic Cancer and their Molecular Characteristics.Scientific reports · 2020Article
- Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats.Journal of analytical methods in chemistry · 2020Article
- Combination Therapy with a PI3K/mTOR Dual Inhibitor and Chloroquine Enhances Synergistic Apoptotic Cell Death in Epstein-Barr Virus-Infected Gastric Cancer Cells.Molecules and cells · 2019Article
- Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-1-regulated apoptosis in pancreatic cancer cells.Cancer biology & therapy · 2019Article
- Metabolic gene alterations impact the clinical aggressiveness and drug responses of 32 human cancers.Communications biology · 2019Article
- Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes.Oncotarget · 2018Article
- Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior antileukemic activity against AML ex vivo.Biochemical pharmacology · 2018Article
- PP242 Counteracts Glioblastoma Cell Proliferation, Migration, Invasiveness and Stemness Properties by Inhibiting mTORC2/AKT.Frontiers in cellular neuroscience · 2018Article
- Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma.Cancer biology & therapy · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease in urgent need of newer therapeutic modalities. Majority of patients with PDAC have mutations in KRAS, which unfortunately remains an ineffectual target. Our strategy here is to target KRAS downstream effectors PI3K and mTOR. In this study, we investigated the antitumor efficacy of the novel PI3K and mTOR dual inhibitor VS-5584 in PDAC. Our data shows that PI3K/mTOR dual inhibition causes ERK activation in all tested PDAC cell lines. Although the MEK inhibitor GSK1120212 could abrogate VS-5584-induced ERK activation, it did not substantially enhance cell death in all the cell lines tested. However, combination with ERK inhibitor SCH772984 not only mitigated VS-5584-induced ERK activation but also enhanced VS-5584-induced cell death. In a xenograft model of PDAC, we observed 28% and 44% tumor inhibition for individual treatment with VS-5584 and SCH772984, respectively, while the combined treatment showed superior tumor inhibition (80%) compared to vehicle control treatment. Our findings support the clinical development of VS-5584 and ERK inhibitor combination for PDAC treatment.
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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.