ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- A computational study of cardiac glycosides from Vernonia amygdalina as PI3K inhibitors for targeting HER2 positive breast cancer.Journal of computer-aided molecular design · 2025Article
- Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
- RASAL2 Deficiency Attenuates Hepatic Steatosis by Promoting Hepatic VLDL Secretion via the AKT/TET1/MTTP Axis.Journal of clinical and translational hepatology · 2023Article
- Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids.Membranes · 2021Review
- Review
- RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo.Biomedicines · 2021Article
- Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis.Scientific reports · 2021Article
- Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- GDC-0326 Enhances the Effects of 5-Fu in Colorectal Cancer Cells by Inducing Necroptotic Death.OncoTargets and therapy · 2021Article
- Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity.Acta pharmacologica Sinica · 2020Review
- Lipid composition of the cancer cell membrane.Journal of bioenergetics and biomembranes · 2020Review
- Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?Frontiers in immunology · 2020Review
- Revisiting PI3-kinase signalling in angiogenesis.Vascular biology (Bristol, England) · 2019Review
- The implications of signaling lipids in cancer metastasis.Experimental & molecular medicine · 2018Review
- Article
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
- The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- The role of PI3Kα isoform in cardioprotection.Basic research in cardiology · 2017Article
- New therapeutic approaches to metastatic gastroenteropancreatic neuroendocrine tumors: A glimpse into the future.World journal of gastrointestinal oncology · 2017Review
- The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.PloS one · 2017Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
purposeMutations in the PI3K pathway occur in 16% of patients with pancreatic neuroendocrine tumors (PanNETs), which suggests that these tumors are an exciting setting for PI3K/AKT/mTOR pharmacologic intervention. Everolimus, an mTOR inhibitor, is being used to treat patients with advanced PanNETs. However, resistance to mTOR-targeted therapy is emerging partially due to the loss of mTOR-dependent feedback inhibition of AKT. In contrast, the response to PI3K inhibitors in PanNETs is unknown. EXPERIMENTAL
designIn the current study, we assessed the frequency of PI3K pathway activation in human PanNETs and in RIP1-Tag2 mice, a preclinical tumor model of PanNETs, and we investigated the therapeutic efficacy of inhibiting PI3K in RIP1-Tag2 mice using a combination of pan (GDC-0941) and p110α-selective (GDC-0326) inhibitors and isoform-specific PI3K kinase-dead-mutant mice.
resultsHuman and mouse PanNETs showed enhanced pAKT, pPRAS40, and pS6 positivity compared with normal tissue. Although treatment of RIP1-Tag2 mice with GDC-0941 led to reduced tumor growth with no impact on tumor vessels, the selective inactivation of the p110α PI3K isoform, either genetically or pharmacologically, reduced tumor growth as well as vascular area. Furthermore, GDC-0326 reduced the incidence of liver and lymph node metastasis compared with vehicle-treated mice. We also demonstrated that tumor and stromal cells are implicated in the antitumor activity of GDC-0326 in RIP1-Tag2 tumors.
conclusionsOur data provide a rationale for p110α-selective intervention in PanNETs and unravel a new function of this kinase in cancer biology through its role in promoting metastasis. Clin Cancer Res; 22(23); 5805-17. ©2016 AACR.
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