ReviewMolecular cancer research : MCR2015
Therapeutic targeting of cellular metabolism in cells with hyperactive mTORC1: a paradigm shift.
Review in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Metabolic Imaging and Molecular Signatures Reveal Metabolic Phenotypes in Recurrent Glioblastoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- The dual role of OTUD3 in cancer: mechanisms and therapeutic implications.Cancer cell international · 2025Review
- Glutaminase - A potential target for cancer treatment.BioMedicine · 2024Review
- Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model.Cell reports. Medicine · 2023Article
- Understanding of black salve toxicity by multi-compound cytotoxicity assays.BMC complementary medicine and therapies · 2022Article
- Perfect match: mTOR inhibitors and tuberous sclerosis complex.Orphanet journal of rare diseases · 2022Review
- Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine.Frontiers in pharmacology · 2022Review
- Imaging dynamic mTORC1 pathway activity in vivo reveals marked shifts that support time-specific inhibitor therapy in AML.Nature communications · 2021Article
- The paradox of autophagy in Tuberous Sclerosis Complex.Genetics and molecular biology · 2021Article
- Glutamine reliance in cell metabolism.Experimental & molecular medicine · 2020Review
- Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma.Cancers · 2020Article
- Glutamine Metabolism Drives Growth in Advanced Hormone Receptor Positive Breast Cancer.Frontiers in oncology · 2019Article
- Tackling tumor heterogeneity and phenotypic plasticity in cancer precision medicine: our experience and a literature review.Cancer metastasis reviews · 2018Review
- Using genetic buffering relationships identified in fission yeast to reveal susceptibilities in cells lacking hamartin or tuberin function.Biology open · 2018Article
- Multinuclear NMR and MRI Reveal an Early Metabolic Response to mTOR Inhibition in Sarcoma.Cancer research · 2017Article
- mTORC1 inhibition in cancer cells protects from glutaminolysis-mediated apoptosis during nutrient limitation.Nature communications · 2017Article
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
- Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies.American journal of medical genetics. Part C, Seminars in medical genetics · 2016Review
- Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses.International journal of molecular sciences · 2016Review
- Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.American journal of obstetrics and gynecology · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
mTORC1 is an established master regulator of cellular metabolic homeostasis, via multiple mechanisms that include altered glucose and glutamine metabolism, and decreased autophagy. mTORC1 is hyperactive in the human disease tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by germline mutations in the TSC1 or TSC2 gene. In TSC-deficient cells, metabolic wiring is extensively disrupted and rerouted as a consequence of mTORC1 hyperactivation, leading to multiple vulnerabilities, including "addiction" to glutamine, glucose, and autophagy. There is synergy between two rapidly evolving trajectories: elucidating the metabolic vulnerabilities of TSC-associated tumor cells, and the development of therapeutic agents that selectively target cancer-associated metabolic defects. The current review focuses on recent work supporting the targeting of cellular metabolic dysregulation for the treatment of tumors in TSC, with relevance to the many other human neoplasms with mTORC1 hyperactivation. These data expose a fundamental paradox in the therapeutic targeting of tumor cells with hyperactive mTORC1: inhibition of mTORC1 may not represent the optimal therapeutic strategy. Inhibiting mTORC1 "fixes" the metabolic vulnerabilities, results in a cytostatic response, and closes the door to metabolic targeting. In contrast, leaving mTORC1 active allows the metabolic vulnerabilities to be targeted with the potential for a cytocidal cellular response. The insights provided here suggest that therapeutic strategies for TSC and other tumors with activation of mTORC1 are at the verge of a major paradigm shift, in which optimal clinical responses will be accomplished by targeting mTORC1-associated metabolic vulnerabilities without inhibiting mTORC1 itself.
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Registered trials
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.