Among different cell cycle regulatory pathways, mTOR pathway is an important one as it is involved in a lot of regulatory activities related to cell proliferation, growth, migration and activities related to transcription and translation. mTOR is actually serine/threonine protein kinase that is a product of FRAP1 gene. Defected or dysregulated mTOR pathway is a common reason of developing cancerous cells. Therefore, these proteins are also targeted while looking for an effective anti-cancer therapy [1]. For this purpose many inhibitors against these proteins are being researched. One of these efficiently acting inhibitors is the Everolimus mTOR inhibitor [2]. It is marketed by pharmaceutical company Novartis and is available under the trade name of Afinitor Everolimus. Everolimus structure is a 40-O-(2-hydroxyethyl) derivative where oxygen at position 40 is known to improve its pharmacokinetic properties. Everolimus IC50 against mTOR is around 1 nM. Everolimus solubility can be achieved upto 100 mg/ml in DMSO. It is also soluble in ethanol and water. Everolimus is an orally administered drug and is available in the form of a vial of 5 mg with an Everolimus price of around $60. It is distributed in dry ice.

One of the properties of Everolimus is its immunosuppressant property in case of cardiac, renal and some of the other transplants, apart from these properties Everolimus is also used for the treatment of different tumors as an effective drug [4] because of its specific ability to check the mTOR1 which leads to stimulation of Akt cascade and inhibits the mTOR2 downstream pathway. Everolimus has been seen to cause the death of cancerous cells by apoptosis whether used as a single agent e.g., against colon cancer [5] or in combination with other drugs like Octreotide against the tumors of neuroendocrine cells where it seems to block Akt-mTOR-p70S6 kinase pathway [6]. Everolimus has also been recently used successfully against renal tumors [7]. The pharmacokinetic properties of the Everolimus have encouraged the scientists to do more research on the drug regarding its efficacy [8].

Everolimus can also be used as stent in cardiac diseases like coronary artery disease or ischemia. The efficiency of Everolimus as stents is being compared with traditionally used stents e., Paclitaxel [9-10]. Everolimus is also being tried to make bioabsorbable stents in order to use it in coronary artery diseases [11].

Everolimus is the best known and most efficacious drug of all the mTOR inhibitors available. It has been used against breast cancer cell lines in In vitro conditions [12] after which the drug was further encouraged to be researched in order to generate more data about the drug [13]. The drug has been studied as a single agent in clinical trial of phase II [15] or as combinations with other chemotherapeutic agents in clinical trial phase I against breast cancer with repeated occurrence [15] or for the patients who are HRP (hormone receptor positive) [16].
The combinatorial therapy has also been studied for the drug against gastric cancer in In vivo models [17]. The results of this research have encouraged for its use in advanced stages of gastric cancer [18] and leading the clinical trial to phase II [19]. Everolimus has also been studied as an immunosuppressing agent after renal transplantations [20]. In a comparative study against renal cancer, Everolimus was found better than Azathioprine [21], the drug used in kidney transplants.
The drug is also efficient for carcinoids treatment where mTOR inhibitor gave good results [22]. In combinatorial therapy, done in clinicl trial phase II the drug was also used with Octreotide against neuroendocrine cancer [23]. Everolimus is considred a unique therapeutic agent that is effective against carcinoids [24] therefore further research is being made on the drug in order to produce more valueable drug.

1. Beevers, C.e.a., Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells. Int J Cancer, 2006. 119(4): p. 757-64.
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3. Eisen, H.J.e.a., Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N. Engl. J. Med., 2003. 349(9): p. 847-58.
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5. Homicsko, e.a., RAD001 (Everolimus) Improves the Efficacy of Replicating Adenoviruses that Target Colon Cancer. Cancer Res, 2005. 65(15): p. 6882-90.
6. Glasberg, S.G.e.a., Octreotide and the mTOR Inhibitor RAD001 (Everolimus) Block Proliferation and Interact with the Akt-mTOR-p70S6K Pathway in a Neuro-Endocrine Tumor Cell Line. Clinical Neuroendocrinology and Neuroendocrine Tumors, 2008  87(3): p. 168-181.
7. Agarwala, e.a., Everolimus (RAD001) in the Treatment of Advanced Renal Cell Carcinoma. The Oncologist, 2010. 15: p. 236-245.
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9. Grube, E.e.a., Six- and Twelve-Month Results From First Human Experience Using Everolimus-Eluting Stents With Bioabsorbable Polymer. Circulation, 2004  109: p. 2168-2171.
10. Stone, G.W.e.a., Comparison of an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients With Coronary Artery Disease. Journal of American Medical Asociation, 2008. 299(16): p. 1903-1913.
11. Ormiston, J.A.e.a., A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. The Lancet, 2008. 371(9616): p. 899-907.
12. Boulay, A.e.a., Dual Inhibition of mTOR and Estrogen Receptor Signaling in vitro Induces Cell Death in Models of Breast Cancer. Clin Cancer Res, 2005(11): p. 5319.
13. Lane, H.A.e.a., Future Directions in the Treatment of Hormone-Sensitive Advanced Breast Cancer: The RAD001 (Everolimus)-Letrozole Clinical Program. Seminars in Oncology, 2006. 33(7): p. 18-25.
14. Awada, A.e.a., The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: Results of a phase I study with pharmacokinetics. European Journal of Cancer, 2008. 44(1): p. 84-91.
15. Ellard, S.L.e.a., Randomized Phase II Study Comparing Two Schedules of Everolimus in Patients With Recurrent/Metastatic Breast Cancer: NCIC Clinical Trials Group IND.163. Journal of Clinical Oncology, 2009. 27(27): p. 4536-4541.
16. Baselga, J.e.a., Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor-Positive Breast Cancer. Journal of Clinical Oncology, 2009  27(16): p. 2630-2637.
17. Cejka, D.e.a., Everolimus (RAD001) and anti-angiogenic cyclophosphamide show long-term control of gastric cancer growth in vivo. Cancer Biol Ther., 2008. 7(9): p. 1377-85.
18. Ajani, J.A.e.a., Evolving Chemotherapy for Advanced Gastric Cancer. The Oncologist, 2005. 10(3): p. 49-58.
19. Doi, T.e.a., Multicenter Phase II Study of Everolimus in Patients With Previously Treated Metastatic Gastric Cancer. Journal of Clinical Oncology, 2010. 28(11): p. 1904-1910.
20. Pascual, J.e.a., Everolimus (Certican) in renal transplantation: a review of clinical trial data, current usage, and future directions. Transplantation Reviews, 2006. 20(1): p. 1-18.
21. Snell, G.I.e.a., Everolimus Versus Azathioprine in Maintenance Lung Transplant Recipients: An International, Randomized, Double-Blind Clinical Trial. American Journal of Transplantation, 2006. 6(1): p. 169-177.
22. Dong, M.a.Y., J.C., mTOR inhibition, a potential novel approach for bronchial carcinoids. Endocr Relat Cancer, 2011. 18: p. C15-C18.
23. Yao, J.C.e.a., Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study. Journal of Clinical Oncology, 2008. 26(26): p. 4311-4318.
24. Zatelli, M.C.e.a., Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids. Endocr Relat Cancer, 2010    17(719-729).
25. Capdevila, J.e.a., Control of carcinoid syndrome with Everolimus. Ann Oncol 2011. 22(1): p. 237-239.

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