{"entity":{"id":"mtor","kind":"target","name":"mTOR","aka":[],"tldr":"mTOR is the cell's master growth controller, deciding whether to build proteins and divide. Rapamycin-like drugs clamp it down in kidney, breast and neuroendocrine cancers and in rare tumours driven by TSC gene loss.","summary":"The mechanistic target of rapamycin is a serine/threonine kinase in two complexes: mTORC1 (with raptor) integrates growth-factor, nutrient and energy signals to control translation via S6K and 4E-BP1, and mTORC2 (with rictor) activates AKT. It is the downstream effector of the PI3K-AKT pathway and is hyperactivated by PIK3CA, PTEN and TSC1/2 alterations. Allosteric mTORC1 inhibitors (rapalogues) are approved: everolimus for renal cell carcinoma, HR-positive breast cancer, neuroendocrine tumours and TSC-associated tumours; temsirolimus for renal cell carcinoma; and albumin-bound sirolimus (Fyarro) for malignant PEComa. ATP-competitive dual mTORC1/2 and PI3K/mTOR inhibitors have not yet reached approval in cancer.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/MTOR","links":[{"label":"NCBI Gene MTOR","url":"https://www.ncbi.nlm.nih.gov/gene/2475"}],"tags":["kinase"],"related":[],"cancers":["rcc","breast-hr-positive","neuroendocrine","sarcoma"],"sections":[],"technologies":["pi3k-akt-mtor-inhibitors"],"targets":[],"drugs":["everolimus","temsirolimus","sirolimus-albumin-bound","sapanisertib"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","choline-metabolism-in-cancer","hepatocellular-carcinoma-signalling","renal-cell-carcinoma-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["mTOR is expressed in all cells and rapalogues are not selected on mTOR status, so the RCC row records the MTOR mutation rate rather than expression. No MTOR-specific series with a stated denominator was found for HR-positive breast cancer, neuroendocrine tumours or sarcoma; Jiao 2011 found mutations in mTOR-pathway genes (PTEN, TSC2, PIK3CA) rather than MTOR itself in 14% of 68 pancreatic neuroendocrine tumours (doi:10.1126/science.1200609)."],"symbol":"MTOR","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists MTOR among essential proteins and finds the RNA at low tissue specificity; the 4 medicines aimed at it (Everolimus, Temsirolimus, Sirolimus protein-bound particles and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA MTOR: RNA low tissue specificity; high antibody staining in 9 normal tissues; highest cancer staining carcinoid (2 of 4 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Renal cell carcinoma, Breast cancer (all types), Neuroendocrine tumours, Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 1 specific cancer type at or above 0.5 (clear cell renal carcinoma). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MTOR tissue","url":"https://www.proteinatlas.org/ENSG00000198793-MTOR/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000198793 associations","url":"https://platform.opentargets.org/target/ENSG00000198793/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3942","ensembl":"ENSG00000198793","uniprot":"P42345","entrez":"2475","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Brown E.J. et al, Nature, 1994, \"A mammalian protein targeted by G1-arresting rapamycin-receptor complex\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8008069/","biology":"Rapalogues bind FKBP12 and allosterically inhibit mTORC1; feedback activation of AKT and incomplete 4E-BP1 inhibition explain modest single-agent activity. Stomatitis, hyperglycaemia, hyperlipidaemia and non-infectious pneumonitis are class effects.","whereFound":["Renal cell carcinoma","HR-positive breast cancer (endocrine resistance)","Pancreatic and lung neuroendocrine tumours","Malignant PEComa and TSC-associated tumours (TSC1/2 loss)"],"targetClass":"kinase","prevalence":[{"cancerId":"rcc","pct":8.2,"measure":"Targeted NGS, MTOR mutation in 184 everolimus-treated RCC patients (RECORD-3)","source":"https://doi.org/10.1158/1078-0432.CCR-18-1833","note":"Voss 2019 (Clin Cancer Res); TSC1 6%, TSC2 4.4%, any PI3K-pathway alteration 44%; mutation status did not predict everolimus benefit"}]},"route":"/targets/mtor/","neighbours":{"cancer":[{"id":"epithelioid-haemangioendothelioma","kind":"cancer","name":"Epithelioid haemangioendothelioma","route":"/cancers/epithelioid-haemangioendothelioma/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"lung-net","kind":"cancer","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/cancers/lung-net/"},{"id":"meningioma","kind":"cancer","name":"Meningioma","route":"/cancers/meningioma/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"pancreatic-net","kind":"cancer","name":"Pancreatic neuroendocrine tumours","route":"/cancers/pancreatic-net/"},{"id":"pecoma","kind":"cancer","name":"Perivascular epithelioid cell tumour (PEComa)","route":"/cancers/pecoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"small-intestinal-net","kind":"cancer","name":"Small intestinal neuroendocrine tumours","route":"/cancers/small-intestinal-net/"}],"technology":[{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"}],"drug":[{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"},{"id":"sapanisertib","kind":"drug","name":"Sapanisertib","route":"/drugs/sapanisertib/"},{"id":"sirolimus","kind":"drug","name":"Sirolimus","route":"/drugs/sirolimus/"},{"id":"sirolimus-albumin-bound","kind":"drug","name":"Sirolimus protein-bound particles","route":"/drugs/sirolimus-albumin-bound/"},{"id":"temsirolimus","kind":"drug","name":"Temsirolimus","route":"/drugs/temsirolimus/"}],"pathway":[{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","route":"/pathways/choline-metabolism-in-cancer/"},{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG map)","route":"/pathways/renal-cell-carcinoma-signalling/"}],"trial":[{"id":"ampect","kind":"trial","name":"AMPECT","route":"/trials/ampect/"},{"id":"tumorapa","kind":"trial","name":"TUMORAPA (switching from a calcineurin inhibitor to sirolimus after a transplant skin cancer)","route":"/trials/tumorapa/"}],"target":[{"id":"fkbp12","kind":"target","name":"FKBP12 (FKBP1A)","route":"/targets/fkbp12/"},{"id":"hif1a","kind":"target","name":"HIF-1α (HIF1A)","route":"/targets/hif1a/"}]}}