Regulatory activities of the cell that are associated with its multiplication, movement, transcription and additionally in translation of the genes is controlled by mTOR pathway that is  among the necessary numerous cell cycle regulators. FRAP1 gene is translated to provide mTOR that phosphorylates serine/threonine residue of proteins. Cancer typically arises from the down-regulation of this mTOR cascade. Therefore for targeted cancer therapy proteins like are also taken into consideration [1]. Different types of inhibitors are being searched and Everolimus mTOR inhibitor is amongst the very promising inhibitors [2]. Novartis that is pharmaceutical company created it and sell it with as Afinitor Everolimus that is its trade name. Since structural studies revealed that Everolimus may be a derivative of 40-O-(2-hydroxyethyl), the pharmacokinetic properties are appeared to be improved owing to the availability of oxygen atom the 40 position. Against mTOR Everolimus IC50 is approximately 1 nM. Around 100 mg/ml of DMSO is appropriate for Everolimus solubility. It is water and ethanol soluble. The mode of administration of Everolimus is via oral route and it is present in 5mg of packaging and approximately $60 is Everolimus price. Dry-ice is used for its distribution.  

Everolimus acts as immunosuppressant in different types of transplantations like heart and kidney transplant. Among other properties of Everolimus it is administered as anti-cancer drug and proved efficient enough [4] by controlling the mTOR1 which ultimately leads to the activation of Akt pathway and causes the inhibition of mTOR2 pathway. When administered alone Everolimus has been shown to cause the programmed cell death of colon cancerous cell [5] or even when it is co-administered with different drugs e.g. Octreotide it revealed to inhibit Akt-mTOR-p70S6 pathway in tumor cells of neuroendocrine [6]. To treat kidney tumors Everolimus is successfully used [7]. The promising results of pharmacokinetics of Everolimus have compelled scientists to evaluate its efficacy in detail [8].

For the treatment of coronary artery disease and ischemia Everolimus can be employed as stents. The conventional stents like Paclitaxel were compared with Everolimus in context of efficiency [9-10]. It has also been tried to make Everolimus a bio-absorbable stent so that it can be used for the treatment of CAD (coronary artery disease) [11].

Among the mTOR inhibitors that are available Everolimus is the most efficient and best. Its effect on cancer cell lines of breast was evaluated [12] which favored to study in detail the effects of drug [13]. It has been evaluated in phase II clinical trials when administered alone [15] and its study is in phase I when it is co-administered in relapsed breast cancer [15]. It is also studied in patients who are reported to be hormone receptor positive [16].The in vivo studies of the medicine against gastric cancer have been reported in combination with other therapies [17].  The results suggested that it can also be employed in the later periods of stomach cancer [18] which continued it to enter the phase II trials [19]. After the kidney is transplanted the effect of Everolimus as immunosuppressant has been reported [20].A comparative study was done to evaluate the efficiency of drug in kidney cancer it showed promising results than Azathioprine [21] which is also used as immunosuppressant in renal transplants.
Everolimus can also be for treatment of carcinoids where good results were shown by mTOR inhibitor [22]. It is co-administered with Octreotide and efficiency was evaluated in phase II clinical trials [23]. Everolimus has proved to be effective therapeutic agent against carcinoids [24] so a lot of research work is being done to develop more effective drug. The drug is also efficient for carcinoids treatment where mTOR inhibitor gave good results [22]. In combinatorial therapy, done in clinical trial phase II the drug was also used with Octreotide against neuroendocrine cancer [23]. Everolimus is considered a unique therapeutic agent that is effective against carcinoids [24] therefore further research is being made on the drug in order to produce more value able 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.
2. Chapman, T.M.a.P., C.M., Everolimus is an immunosuppressant analog of rapamycin (sirolimus) and inhibits growth factor-mediated proliferation of haematopoietic and nonhaematopoietic cells. Drugs, 2004. 64: p. 861-874.
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.
4. Faivre, S.e.a., Current development of mTOR inhibitors as anticancer agents. Nature Reviews Drug Discovery, 2006. 5: p. 671-688.
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.
8. Kirchner, G.I.e.a., Clinical Pharmacokinetics of Everolimus. Clinical Pharmacokinetics, 2004. 43(2): p. 83-95.
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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