mTOR belongs to phosphatidylinositol 3-kinase family which are the protein kinases that regulate cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Due to the involvement of these in above mentioned processes they have gained importance from therapy point of view in cancer treatment. In comparison to Rapamycin Temsirolimus mTOR inhibitor gained importance for the past few years.

Temsirolimus Torisel is one of those few inhibitors which are now on waiting list for an authorization from FDA for the treatment of renal cell carcinoma or RCC. Wyeth is developing Temsirolimus 162635-04-3 and it is given as intravenous injection to patients. Temsirolimus is also known as CCI-779. Anyone can purchase Temsirolimus from Temsirolimus supplier as Torisol at the rate of $100 per 200mg of packaging. Temsirolimus structure share structural similarity with Sirolimus. It is insoluble in water while the Temsirolimus solubility is around 200 mg/mL in DMSO and ethanol. Temsirolimus is stable at -20ºC even for two years. Its cost varies according to rate of purity of salt.


Temsirolimus CCI-779 has the same mode of action as different other mTOR inhibitor molecules [1]. During past few years different types of cancer and specially disease called Pompe are being cured by giving Temsirolimus. Temsirolimus function is actually to make the cells of the patients sensitive to SCLC or Cisplatin therapy as those cells were resistant to Cisplatin small cell lung cancer[4]. After assessing it completely and getting proper evidences its anti-angiogenic effects in in-vitro and in-vivo both models, Temsirolimus has been used as a good and remarkable anti-angiogenic agent.
Temsirolimus has proved itself in xenograft models of rhabdomyosarcoma as an anti-angiogenic drug [6]. Outstanding results were demonstrated by Temsiroimus against preclinical models of mammary tumors [8] and against cancer of breast it being given as combination with other medicines [7]. The Temsirolimus safety profile was studied in patients of metastasis [9] and advanced renal cell carcinoma [10] and this information was used in the clinical trials phase I and phase II in the combination of Interferon-alpha.


Combinatorial therapies were conducted in clinical trials phase I against different types of cancers [14] after pharmacokinetic properties being evaluated for phase I [13]. Different other combinations were used as well in clinical trials phase I against the advance breast carcinoma and gynecologic malignancies, and it was also seen that Temsirolimus alone is very effective against breast cancer patients under clinical trials phase II [16]. When solid tumors were treated with Temsirolimus it showed outstanding results [17] either by giving alone or in combination [18]. It has also got approval against the pediatric patients [19]. Temsirolimus has also exhibited remarkable results in phase II clinical trials of NSCLC [20].
Temsirolimus clinical trials on mantle cell lymphoma patients gave most promising results. In clinical trials of phase II very low dosage was given [21] and in combination with other medicines [22]. The fruitful results given by Temsirolimus encouraged scientists to carry out phase III trials of mantle cell lymphoma and again it gave good results [23]. Phase II clinical studies against ovarian cancer [24], endometrium malignancy [25], neuroendocrine cancer [27], soft tissue sarcoma [26], and the most important glioblastoma [28] were carried out as well, where it has shown promising results.

1. Rini, B.I.e.a., Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin. Clin Cancer Res, 2008.
2. Dancey, J.E.e.a., Evaluating Temsirolimus Activity in Multiple Tumors: A Review of Clinical Trials. Seminars in Oncology, 2009.
3. Ashe, K.M.e.a., Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease. Molecular Genetics and Metabolism, 2010.
4. Wu, C.e.a., Overcoming cisplatin resistance by mTOR inhibitor in lung cancer. Mol. Cancer, 2005.
5. Del Bufalo, D.e.a., Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus. Cancer Res., 2006.
6. Wan, X.e.a., CCI-779 inhibits rhabdomyosarcomaxenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling. Neoplasia, 2006.
7. Sadler, T.M.e.a., Combination therapy for treating breast cancer using antiestrogen, ERA-923, and the mammalian target of rapamycin inhibitor, temsirolimus. EndocrRelat Cancer, 2006  
8. Wang, X.e.a., Multi-Modal Biomarker Investigation on Efficacy and Mechanism of Action for the mTOR inhibitor, Temsirolimus, in a Preclinical Mammary Carcinoma Oncomouse (PyMT) Model: A Translational Medicine Study in Support for Early Clinical Development. Journal of Pharmacology and Experimental Therapeutics, 2011.
9. Lamm, W.e.a., Safety and efficacy of temsirolimus in heavily pretreated patients with metastatic renal cell carcinoma. ActaOncologica, 2011.
10. Bellmunt, J.e.a., Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Oncol., 2008.
11. Grundbichler, M.e.a., Efficacy of Temsirolimus after Previous Treatment with Sunitinib, Sorafenib or Everolimus in Advanced Renal Cell Cancer. Oncology, 2011.
12. Motzer, R.J.e.a., Phase I/II Trial of Temsirolimus Combined With Interferon Alfa for Advanced Renal Cell Carcinoma. Journal of Clinical Oncology, 2007.
13. Hidalgo, M.e.a., A Phase I and Pharmacokinetic Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients with Advanced Cancer. Clin Cancer Res, 2006.
14. Naing, A.e.a., Phase I Trial of Cixutumumab Combined with Temsirolimus in Patients with Advanced Cancer. Clinical Cancer Research, 2011.
15. Moroney, J.W., A Phase I Trial of Liposomal Doxorubicin, Bevacizumab and Temsirolimus in Patients with Advanced Gynecologic and Breast Malignancies. Clinical Cancer Research, 2011.
16. Chan, S.e.a., Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer. Journal of Clinical Oncology, 2005.
17. MacKenzie, M.J.e.a., A phase I study of temsirolimus and metformin in advanced solid tumours. Investigational New Drugs, 2010.
18. Kollmannsberger, C.e.a., Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179). Ann Oncol., 2011.
19. Spunt, S.L.e.a., Phase I Study of Temsirolimus in Pediatric Patients With Recurrent/Refractory Solid Tumors. Journal of Clinical Oncology, 2011.
20. Pandya, K.e.a., A Randomized, Phase II Trial of Two Dose Levels of Temsirolimus (CCI-779) in Patients with Extensive-Stage Small-Cell Lung Cancer Who Have Responding or Stable Disease after Induction Chemotherapy: A Trial of the Eastern Cooperative Oncology Group (E1500). Journal of Thoracic Oncology, 2007.
21. Ansell, S.M.e.a., Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma. Cancer, 2008.
22. Ansell, S.M.e.a., Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. The Lancet Oncology, 2011.
23. Hess, G.e.a., Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma. Journal of Clinical Oncology, 2009.
24. Behbakht, K.e.a., Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study. Gynecologic Oncology, 2011.
25. Oza, A.M.e.a., Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group. Journal of Clinical Oncology, 2011.
26. Okuno, S.e.a., A phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas. Cancer, 2011.
27. Duran, I.e.a., A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal of Cancer, 2006.
28. Galanis, E.e.a., Phase II Trial of Temsirolimus (CCI-779) in Recurrent GlioblastomaMultiforme: A North Central Cancer Treatment Group Study. Journal of Clinical Oncology, 2005.

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