Prostate cancer
Cancer in which oncogenic mTOR signaling reprograms the cell's translation to drive proliferation, invasion and metastasis.
A cancer where mTORC2 matters unusually much. A cancer in which mTOR signaling gets hijacked to rev up a tumor's protein-building machinery, helping it grow, invade nearby tissue, and spread.
Rictor deletion blocks PTEN-null prostate tumorigenesis in mice; rapalog monotherapy has not translated, consistent with an mTORC2-dependent mechanism.
TL;DR. Prostate cancer appears in 3 curated studies in Oliver's mTOR Atlas: 2 in animal models; 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| mTORC1 activates Prostate cancer mechanism: functional-consequence · this link in full · on the map table | Blocking mTOR reversed early, pre-cancerous prostate changes in mice caused by an overactive growth signal. Blocking mTOR reversed Akt-driven pre-cancerous prostate lesions in mice, showing the growth was mTORC1-dependent and reversible. Blocking mTOR reversed Akt-driven pre-cancerous prostate lesions in mice, showing the growth was mTORC1-dependent and reversible. Holds under: Scope: the lesion was prostatic intraepithelial neoplasia, a pre-cancerous stage, driven by transgenic human AKT1 in mice, and the drug (RAD001) inhibits mTORC1 allosterically. Mouse only in this corpus. Not a demonstration in established prostate cancer. plausible in people, not shown directly · emerging, few independent studies | A | MAJ2004 |
| mTORC2 required-for Prostate cancer mechanism: functional-consequence · this link in full · on the map table | Prostate tumours caused by losing a specific tumour-suppressor gene (Pten) need mTORC2 to develop – normal prostate tissue doesn't, at least in mice. Prostate cancer driven by Pten loss needs mTORC2 to develop; normal prostate does not. A real therapeutic window, at least in mice. Prostate cancer driven by Pten loss needs mTORC2 to develop; normal prostate does not. A real therapeutic window, at least in mice. Holds under: Single-study edge in this corpus (GUE2009). Shown in Pten-null mouse prostate only: mTORC2 (Rictor) is required for tumours to develop in that genetic background, while normal prostate epithelium is not dependent on it. Mouse only - not tested in another species in this corpus, and not shown in human prostate cancer. plausible in people, not shown directly · emerging, few independent studies | A | GUE2009 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 2 |
| M | Molecular — cells, biochemistry, structure | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2009 | A | mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice GUE2009 mTORC2 is required for prostate cancer driven by Pten loss in mice. |
| 2004 | A | mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways MAJ2004 mTOR inhibition (rapamycin/RAD001) reverses Akt-driven prostate intraepithelial neoplasia in mice. |
| 2012 | M | The translational landscape of mTOR signalling steers cancer initiation and metastasis HSI2012 Showed WHY mTOR-driven translation matters for cancer: in prostate cancer, oncogenic mTOR selectively translates a specific set of pro-invasion mRNAs that drive metastasis. An ATP-competitive mTOR inhibitor (INK128) reversed that signature - an early preclinical rationale from mouse models and cell lines, not a clinical result. |
Related entities
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