mTOR
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Rapalogues bind FKBP12 and allosterically inhibit mTORC1; feedback activation of AKT and incomplete 4E-BP1 inhibition explain modest single-agent activity.
- 3 · How drugs use it
1 product aims 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.
Elsewhere
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.
- Renal cell carcinoma
- HR-positive breast cancer (endocrine resistance)
- Pancreatic and lung neuroendocrine tumours
- Malignant PEComa and TSC-associated tumours (TSC1/2 loss)
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetAKT
Shares Everolimus, PI3K / AKT / mTOR, Neuroendocrine tumours, Renal cell carcinoma and the tag kinase.
- TargetCDK4/6
Shares Sarcomas (soft tissue, bone, GIST), HR-positive / HER2-negative breast cancer and the tag kinase.
- TargetBTK (Bruton tyrosine kinase)
Shares PI3K / AKT / mTOR and the tag kinase.
- TargetPIK3CA / PI3K-alpha
Shares Everolimus, PI3K / AKT / mTOR, HR-positive / HER2-negative breast cancer and the tag kinase.
- TargetKIT
Shares PI3K / AKT / mTOR, Sarcomas (soft tissue, bone, GIST) and the tag kinase.
- TargetROS1
Shares PI3K / AKT / mTOR and the tag kinase.
- TargetFGFR2
Shares PI3K / AKT / mTOR and the tag kinase.
- TargetALK
Shares PI3K / AKT / mTOR and the tag kinase.