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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.
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.
In plain words · 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.
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.
Rapalogues bind FKBP12 and allosterically inhibit mTORC1; feedback activation of AKT and incomplete 4E-BP1 inhibition explain modest single-agent activity.
3 products aim at mTOR: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: Human Protein Atlas MTOR tissue; Open Targets ENSG00000198793 associations
First described 1994. 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". Source.
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.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Breast, Bronchus, Caudate, Cerebral cortex, Cervix, Colon, Endometrium.
Medium only: breast cancer, cervical cancer, endometrial cancer, glioma.
HPA MTOR tissue · HPA MTOR pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Renal cell carcinoma | 8.2% | Targeted NGS, MTOR mutation in 184 everolimus-treated RCC patients (RECORD-3) | Voss 2019 (Clin Cancer Res); TSC1 6%, TSC2 4.4%, any PI3K-pathway alteration 44%; mutation status did not predict everolimus benefit | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Sapanisertib is an experimental small-molecule drug from Faeth Therapeutics in phase 2 trials for HR-positive / HER2-negative breast cancer and endometrial cancer, aimed at mTOR.
Sirolimus is an anti-rejection tablet taken after an organ transplant. Switching to it from a calcineurin inhibitor roughly halves the number of new skin squamous cell carcinomas in people who have already had one, at the cost of more side effects and a quarter of people stopping it.
Fyarro is an infusion of the transplant drug sirolimus packaged in albumin particles. It is the first approved treatment for malignant PEComa, a rare soft-tissue tumour driven by loss of the TSC genes.
Query for this target: (TITLE:"mTOR" OR ABSTRACT:"mTOR" OR TITLE:"MTOR" OR ABSTRACT:"MTOR") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about mTOR, not a curated reading list.
Shares PI3K, AKT and mTOR inhibitors, Everolimus, PI3K / AKT / mTOR, Neuroendocrine tumours and the tag kinase.
Shares Epithelioid haemangioendothelioma and the tag kinase.
Shares Sarcomas (soft tissue, bone, GIST), HR-positive / HER2-negative breast cancer and the tag kinase.
Shares PI3K / AKT / mTOR and the tag kinase.
Shares PI3K, AKT and mTOR inhibitors, Everolimus, PI3K / AKT / mTOR, HR-positive / HER2-negative breast cancer and the tag kinase.
Shares PI3K / AKT / mTOR, Sarcomas (soft tissue, bone, GIST) and the tag kinase.
Shares PI3K / AKT / mTOR and the tag kinase.
Shares PI3K / AKT / mTOR and the tag kinase.