Pathway link EVE-MTORC1
Everolimus mTORC1
Everolimus inhibits mTORC1.
Everolimus is rapamycin with a small chemical tweak that makes it easier to take as a pill – same mechanism, better drug.
The conditions it holds under
Clinical evidence from phase 3 trials of everolimus in specific diseases (kidney cancer, breast cancer, pancreatic neuroendocrine tumours, TSC and LAM) at the doses used for those diseases. It does not speak to low-dose use in healthy ageing.
- Time it takes
- hours
- Step
- indirect (through steps not drawn here)
- Measured in
- human
- Where in the cell
- lysosome
- Reaches people?
- shown in people
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2008 | H | Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trialMOT2008 Everolimus extended median progression-free survival from 1.9 to 4.0 months versus placebo in metastatic renal cell carcinoma. |
| 2011 | H | Everolimus for advanced pancreatic neuroendocrine tumors (RADIANT-3)YAO2011 A phase 3 RCT (n=410) that made everolimus a standard treatment for pancreatic neuroendocrine tumors. It more than doubled progression-free survival (11.0 vs 4.6 months, a 65% reduction in risk of progression/death) with mostly mild side effects. Another FDA-approved indication built on blocking mTOR. |
| 2012 | H | Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (BOLERO-2)BAS2012 A phase 3 RCT (n=724) proving mTOR matters in a common cancer. Resistance to hormone therapy in breast cancer is associated with mTOR activation. Adding everolimus more than doubled progression-free survival (10.6 vs 4.1 months by central review) - leading to FDA approval. Main toxicity was stomatitis. |
| 2010 | H | Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosisKRU2010 In patients whose TSC1/TSC2 mutations cause brain tumors, everolimus shrank tumor volume by 30%+ in three-quarters of patients. Open-label and uncontrolled (n=28); randomised confirmation came later (FRA2013). |
| 2013 | H | Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trialBIS2013 The companion phase 3 RCT (n=118) to EXIST-1, targeting kidney tumors (angiomyolipomas) in tuberous sclerosis and LAM. Everolimus shrank them by >=50% in 42% of patients versus 0% on placebo. Together EXIST-1 and -2 sealed everolimus as a disease-modifying therapy across multiple TSC tumor types. |
| 2012 | H | Genome sequencing identifies a basis for everolimus sensitivityIYE2012 Genome sequencing of a single exceptional everolimus responder implicates TSC1 loss as the sensitivity basis. An n-of-1 observation, hypothesis-generating rather than confirmatory. |
| 2008 | A | Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and functionMEI2008 mTOR inhibition rescues a neuronal tuberous-sclerosis model, supporting rapamycin for TSC neurology. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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