mTor Inhibitors for the Treatment of Endometriosis

We read with great interest the article of Kacan et al. entitled “Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat Study” [1] published in your journal.

The authors surgically induced endometriosis by the autotransplantation of uterine tissue in the peritoneal cavity of 24 rats. The animals were randomized in three groups, receiving oral everolimus, oral anastrozole, or intravenous saline solution for 14 days. Histological evaluation was done by the endometriosis score (according to Keenan et al. [2]) and immunohistochemical examination was performed by using antibodies against vascular endothelial growth factor (VEGF), CD117 and BAX. The post-treatment analysis of endometriotic implants revealed that anastrozole and everolimus succeeded in significantly decreasing their growth and size with no difference in histological and immunohistochemical results between the two drugs. The authors noted at histology that the number of ovarian follicles was not negatively altered by everolimus, differently from anastrozole that, as evidenced in literature, tends to decrease it [3].

• References

• 1 Kacan T, Yildiz C, Baloglu Kacan S. et al. Everolimus as an mTOR inhibitor suppresses endometriotic implants: an experimental rat study. Geburtsh Frauenheilk 2017; 77: 66-72
• 2 Keenan JA, Williams-Boyce PK, Massey PJ. et al. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril 1999; 72: 135-141
• 3 Oral E, Demir B, Inceboz U. Endometriosis and ovarian reserve. Womens Health (Lond) 2015; 11: 671-675
• 4 Cinar O, Seval Y, Uz YH. et al. Differential regulation of Akt phosphorylation in endometriosis. Reprod Biomed Online 2009; 19: 864-871
• 5 Leconte M, Nicco C, Ngo C. et al. The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice. Am J Pathol 2011; 179: 880-889
• 6 Wesolowski R, Abdel-Rasoul M, Lustberg M. et al. Treatment-related mortality with everolimus in cancer patients. Oncologist 2014; 19: 661-668
• 7 Gajate P, Alonso-Gordoa T, Martinez-Saez O. et al. Prognostic and predictive role of the PI3K-AKT-mTOR pathway in neuroendocrine neoplasms. Clin Transl Oncol 2017;
• 8 Pallet N, Legendre C. Adverse events associated with mTOR inhibitors. Expert Opin Drug Saf 2013; 12: 177-186