ArticleCell reports2015
Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Unraveling Extremely DamagingJournal of personalized medicine · 2023Article
- MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.The Journal of experimental medicine · 2023Article
- Discovering new biology with drug-resistance alleles.Nature chemical biology · 2021Review
- Article
- SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer.Nature communications · 2021Article
- Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis.Cell reports · 2021Article
- Rheb1-Independent Activation of mTORC1 in Mammary Tumors Occurs through Activating Mutations in mTOR.Cell reports · 2020Article
- Type 2 Diabetes, Obesity, and Cancer Share Some Common and Critical Pathways.Frontiers in oncology · 2020Review
- Sorafenib and Carfilzomib Synergistically Inhibit the Proliferation, Survival, and Metastasis of Hepatocellular Carcinoma.Molecular cancer therapeutics · 2018Article
- ICBS 2017 in Shanghai-Illuminating Life with Chemical Innovation.ACS chemical biology · 2018Article
- SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.Molecular cell · 2018Article
- A system to identify inhibitors of mTOR signaling using high-resolution growth analysis in Saccharomyces cerevisiae.GeroScience · 2017Article
- How to tackle antimalarial resistance?EMBO molecular medicine · 2017Article
- PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer.EBioMedicine · 2015Article
- Aberrant amino acid signaling promotes growth and metastasis of hepatocellular carcinomas through Rab1A-dependent activation of mTORC1 by Rab1A.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinases are therapeutic targets for human cancer. However, "gatekeeper" mutations in tyrosine kinases cause acquired clinical resistance, limiting long-term treatment benefits. mTOR is a key cancer driver and drug target. Numerous small-molecule mTOR kinase inhibitors have been developed, with some already in human clinical trials. Given our clinical experience with targeted therapeutics, acquired drug resistance in mTOR is thought likely, but not yet documented. Herein, we describe identification of a hot spot (L2185) for drug-resistant mutations, which is distinct from the gatekeeper site, and a chemical scaffold refractory to drug-resistant mutations. We also provide new insights into mTOR kinase structure and function. The hot spot mutations are potentially useful as surrogate biomarkers for acquired drug resistance in ongoing clinical trials and future treatments and for the design of the next generation of mTOR-targeted drugs. Our study provides a foundation for further research into mTOR kinase function and targeting.
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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.