ArticleMolecular cancer therapeutics2012
Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A High-Throughput Screening Platform Identifies Novel Combination Treatments for Malignant Peripheral Nerve Sheath Tumors.Molecular cancer therapeutics · 2022Article
- Review
- Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma.Frontiers in pharmacology · 2021Review
- Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.Current research in pharmacology and drug discovery · 2021Review
- The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.Cancers · 2019Review
- 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
- Targeting autophagy potentiates antitumor activity of Met-TKIs against Met-amplified gastric cancer.Cell death & disease · 2019Article
- Article
- Dual PI3K/mTOR Inhibitor, XL765, suppresses glioblastoma growth by inducing ER stress-dependent apoptosis.OncoTargets and therapy · 2019Article
- Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor.Cancer medicine · 2018Article
- Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors.Oncotarget · 2018Article
- A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery.Scientific reports · 2017Article
- Regulation of multidrug resistance by microRNAs in anti-cancer therapy.Acta pharmaceutica Sinica. B · 2017Review
- Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Autophagy inhibition enhances colorectal cancer apoptosis induced by dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235.Oncology letters · 2016Article
- Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.Cell death & disease · 2015Article
- Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy.Autophagy · 2015Review
- Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice.PloS one · 2015Article
- Increased drug resistance is associated with reduced glucose levels and an enhanced glycolysis phenotype.British journal of pharmacology · 2014Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer clinical trials, was tested in two human MPNST xenograft models (STS26T and MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765 abrogated human MPNST local and metastatic growth in severe combined immunodeficient mice. Notably, this therapeutic approach failed to induce apoptosis in MPNST cells but rather resulted in marked productive autophagy. Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic regimen of MPNST xenografts after pretreatment with XL765 resulted in superior antitumor effects as compared with either agent alone. Together, preclinical studies described here expand our previous findings and suggest that PI3K/mTOR inhibition alone and (most importantly) in combination with autophagy blockade may comprise a novel and efficacious therapy for patients harboring MPNST.
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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.