TORISEL Mechanism of Action
TORISEL is an mTOR inhibitor1
- The mammalian target of rapamycin (mTOR) is an intracellular protein that has been implicated in multiple growth-related cellular functions2
- TORISEL is an inhibitor of mTOR1
- TORISEL binds to an intracellular protein, FKBP12, and the protein-drug complex inhibits the activity of mTOR that controls cell division.1
- The inhibition of mTOR prevents the transcription of mRNAs and translation of proteins required for cell cycle progression from G1 to S phase by mediating the activation of p70S6K and 4E-BP12
- Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells1
- In in vitro studies using renal cell carcinoma cell lines, TORISEL inhibited the activity of mTOR and resulted in reduced expression of hypoxia-inducible factors HIF-1α and HIF-2α and vascular endothelial growth factor (VEGF).1
The mTOR pathway2
mTOR functions as an important regulator of cell proliferation, cell growth, and cell survival.2,3
The accumulation of HIF-1α leads to the subsequent over-expression and increased levels of VEGF, which promotes angiogenesis.4,5
mTOR Pathway Video
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Patient Education Materials
Give your patients and their caregivers information about renal cell carcinoma and TORISEL.
References:
- TORISEL® Kit (temsirolimus) Prescribing Information, Wyeth Pharmaceuticals Inc.
- Adjei AA, Hidalgo M. Intracellular signal transduction pathway proteins as targets for cancer therapy. J Clin Oncol. 2005;23:5386-5403.
- Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003;3:371-377.
- Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003;170:2163-2172.
- Tee AR, Blenis J. mTOR, translational control and human disease. Semin Cell Dev Biol. 2005;16:29-37.
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