ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Cotargeting the PI3K and RAS pathways for the treatment of neuroendocrine tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- Machine learning based predictive model and genetic mutation landscape for high-grade colorectal neuroendocrine carcinoma: a SEER database analysis with external validation.Frontiers in oncology · 2025Article
- Carcinoid Syndrome: Preclinical Models and Future Therapeutic Strategies.International journal of molecular sciences · 2023Review
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- Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects.Cancers · 2022Article
- RUNDC3A/SNAP25/Akt signaling mediates tumor progression and chemoresistance in gastric neuroendocrine carcinoma.Cell death & disease · 2022Article
- Review
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- Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.OncoTargets and therapy · 2019Article
- Article
- Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.Cancer science · 2018Article
- The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines.Endocrine-related cancer · 2018Article
- Molecular challenges of neuroendocrine tumors.Oncology letters · 2018Article
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
- PI3K inhibitor enhances the cytotoxic response to etoposide and cisplatin in a newly established neuroendocrine cervical carcinoma cell line.Oncotarget · 2017Article
- Article
- A New View of Pathway-Driven Drug Resistance in Tumor Proliferation.Trends in pharmacological sciences · 2017Review
- The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.PloS one · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe precise involvement of the PI3K/mTOR and RAS/MEK pathways in carcinoid tumors is not well defined. Therefore, the purpose of our study was to evaluate the role these pathways play in carcinoid cell proliferation, apoptosis, and secretion and to determine the effects of combined treatment on carcinoid tumor inhibition.
methodsThe human neuroendocrine cell lines BON (pancreatic carcinoid), NCI-H727 (lung carcinoid), and QGP-1 (somatostatinoma) were treated with either the pan-PI3K inhibitor, BKM120, or the dual PI3K-mTOR inhibitor, BEZ235, alone or in combination with the MEK inhibitor, PD0325901; proliferation, apoptosis, and protein expression were assessed. Peptide secretion was evaluated in BON and QGP-1 cells. The antiproliferative effect of BEZ235, alone or combined with PD0325901, was then tested in vivo.
resultsBoth BKM120 and BEZ235 decreased proliferation and increased apoptosis; combination with PD0325901 significantly enhanced the antineoplastic effects of either treatment alone. In contrast, neurotensin peptide secretion was markedly stimulated with BKM120 treatment, but not BEZ235. The combination of BEZ235 + PD0325901 significantly inhibited the growth of BON xenografts without systemic toxicity.
conclusionsBoth BKM120 and BEZ235 effectively inhibited neuroendocrine tumor (NET) cell proliferation and stimulated apoptosis. However, inhibition of the PI3K pathway alone with BKM120 significantly stimulated neurotensin peptide secretion; this did not occur with the dual inhibition of both PI3K and mTOR using BEZ235 suggesting that this would be a more effective treatment regimen for NETs. Moreover, the combination of BEZ235 and the MEK inhibitor PD0325901 was a safe and more effective therapy in vivo compared with single agents alone.
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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.