ArticleBritish journal of cancer2009
Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The trial behind it
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Who cites it
60 citing papers in PubMed, 124 citations in OpenAlex.
- Epitranscriptomic regulation of NVP-BEZ235 resistance in ccRCC via the YTHDF3-SYNM regulatory pathway.Genes & genomics · 2026Article
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?Therapeutic advances in medical oncology · 2024Review
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2).Cells · 2022Article
- Review
- Curcumin-induced promoter hypermethylation of the mammalian target of rapamycin gene in multiple myeloma cells.Oncology letters · 2019Article
- Antitumor efficacy of liposome-encapsulated NVP-BEZ 235 in combination with irreversible electroporation.Drug delivery · 2018Article
- Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats.Hormones & cancer · 2018Article
- MTOR inhibitor-based combination therapies for pancreatic cancer.British journal of cancer · 2018Article
- Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy.OncoTargets and therapy · 2018Article
- Preprogramming therapeutic response of PI3K/mTOR dual inhibitor via the regulation of EHMT2 and p27 in pancreatic cancer.American journal of cancer research · 2018Article
- Combined treatment of pancreatic cancer xenograft withWorld journal of gastroenterology · 2017Article
- Evolving Significance and Future Relevance of Anti-Angiogenic Activity of mTOR Inhibitors in Cancer Therapy.Cancers · 2017Review
- A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib (BEZ235) Combined with Everolimus in Patients with Advanced Solid Malignancies.Targeted oncology · 2017Article
- Deciphering the link between PI3K and PAK: An opportunity to target key pathways in pancreatic cancer?Oncotarget · 2017Review
- GSK3β-dependent cyclin D1 and cyclin E1 degradation is indispensable for NVP-BEZ235 induced G0/G1 arrest in neuroblastoma cells.Cell cycle (Georgetown, Tex.) · 2017Article
- Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC.Oncotarget · 2016Article
- Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models.BMC cancer · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway is frequently deregulated in pancreatic cancers, and is believed to be an important determinant of their biological aggression and drug resistance. NVP-BEZ235 is a novel, dual class I PI3K/mammalian target of rapamycin (mTor) inhibitor undergoing phase I human clinical trials. To simulate clinical testing, the effects of NVP-BEZ235 were studied in five early passage primary pancreatic cancer xenografts, grown orthotopically. These tumours showed activated PKB/Akt, and increased levels of at least one of the receptor tyrosine kinases that are commonly activated in pancreatic cancers. Pharmacodynamic effects were measured following acute single doses, and anticancer effects were determined in separate groups following chronic drug exposure. Acute oral dosing with NVP-BEZ235 strongly suppressed the phosphorylation of PKB/Akt, followed by recovery over 24 h. There was also inhibition of Ser235/236 S6 ribosomal protein and Thr37/46 4E-BP1, consistent with the effects of NVP-BEZ235 as a dual PI3K/mTor inhibitor. Chronic dosing with 45 mg kg(-1) of NVP-BEZ235 was well tolerated, and produced significant tumour growth inhibition in three models. These results predict that agents targeting the PI3K/Akt/mTor pathway might have anticancer activity in pancreatic cancer patients, and support the testing of combination studies involving chemotherapy or other molecular targeted agents.
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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.