ArticleCancer research2016
mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Boronates as hydrogen peroxide-reactive warheads in the design of detection probes, prodrugs, and nanomedicines used in tumors and other diseases.Drug delivery and translational research · 2023Review
- A case report of lymphangioleiomyomatosis with retroperitoneal masses in pregnancy.Frontiers in medicine · 2023Article
- Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM).Cell death & disease · 2022Article
- Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.EMBO molecular medicine · 2021Article
- Therapeutic Targeting of DGKA-Mediated Macropinocytosis Leads to Phospholipid Reprogramming in Tuberous Sclerosis Complex.Cancer research · 2021Article
- Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex.Orphanet journal of rare diseases · 2020Article
- Ornithine decarboxylase, the rate-limiting enzyme of polyamine synthesis, modifies brain pathology in a mouse model of tuberous sclerosis complex.Human molecular genetics · 2020Article
- Gamma-Glutamyltransferase 1 Promotes Clear Cell Renal Cell Carcinoma Initiation and Progression.Molecular cancer research : MCR · 2019Article
- Inhibition of mTORC1 in pediatric low-grade glioma depletes glutathione and therapeutically synergizes with carboplatin.Neuro-oncology · 2019Article
- Renal disease in tuberous sclerosis complex: pathogenesis and therapy.Nature reviews. Nephrology · 2018Review
- Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression.Science advances · 2018Article
- Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency.Cancer cell · 2017Article
- p62/SQSTM1 Cooperates with Hyperactive mTORC1 to Regulate Glutathione Production, Maintain Mitochondrial Integrity, and Promote Tumorigenesis.Cancer research · 2017Article
- Rapamycin (mTORC1 inhibitor) reduces the production of lactate and 2-hydroxyglutarate oncometabolites in IDH1 mutant fibrosarcoma cells.Journal of experimental & clinical cancer research : CR · 2017Article
- Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation.Cancer research · 2017Article
- Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer.Oncotarget · 2017Article
- Two is better than one; toward a rational design of combinatorial therapy.Current opinion in structural biology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. Cancer Res; 76(16); 4816-27. ©2016 AACR.
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