Temsirolimus is the active ingredient sold under the brand name of drug Torisel®, which has been approved in some countries for the treatment of renal cell carcinoma (RCC).[Note: Temsirolimus sold by Gene Operation is for scientific research use only, not for human and veterinary use.]
Temsirolimus (CCI-779), a dihydroxymethyl propionic acid ester of rapamycin, is an effective inhibitor of mTOR developed for intravenous use in cancer chemotherapy. CCI-779 has displayed anticancer activity alone or in combination with cytotoxic agents in a variety of preclinical models such as glioblastoma, rhabdomyosarcoma, neuroectodermal tumour such as prostate, pancreatic and breast cancer cells [1-3] and is being evaluated in phase II clinical trials for some cancers [4-5]. In a panel of eight breast cancer lines, six of which are sensitive (IC50 ≤50 nM) and two lines are resistant (IC50>1.0 μM) to CCI-779. Sensitive lines are estrogen dependent (MCF-7, BT-474, T-47D), or lacked expression of the tumor suppressor PTEN (MDA-MB-468, BT-549), and/or overexpressed the Her-2/neu oncogene (SKBR-3, BT-474). Resistant lines (MDA-MB-435,MDA-MB-231) share none of these properties. CCI-779 (50 nM) suppresses mTOR function in both a sensitive and a resistant line [6]. In combination with MOR antagonist Methylnaltrexone (MNTX), CCI-779 enhances inhibition of VEGF-induced EC proliferation and migration with an IC50shift from ~10 nM to ~1 nM and from ~50 to ~10 nM respectively [7]. A p70(s6) kinase assay in PBMCs is currently being incorporated in Phase I and II studies with CCI-779 to determine its relationship with dose and plasma concentration of the agent and its value as a predictor of treatment efficacy [8].