mTor Inhibitors for the Treatment of Endometriosis

Fabio Barra, Simone Ferrero
Geburtshilfe und Frauenheilkunde · 2018 · vol. 78(03) , pp. 283–284 · doi:10.1055/s-0043-124518 · PMID:29576633 · W2790377547
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This experimental rat study investigated the efficacy of the mTOR inhibitor everolimus in suppressing endometriotic implants.

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This letter comments on an experimental rat study in which 24 rats with surgically induced peritoneal endometriosis received oral everolimus, oral anastrozole, or intravenous saline for 14 days, with outcomes assessed by endometriosis scores and immunohistochemistry for VEGF, CD117, and BAX. The underlying study reported that anastrozole and everolimus both significantly decreased implant growth and size with broadly similar histologic and immunohistochemical findings, while everolimus did not negatively affect ovarian follicles, unlike anastrozole. The letter’s authors raise concerns about translating mTOR inhibition to endometriosis because of the lack of validated predictive biomarkers, the limited peritoneal localization of the induced implants (relative to deep infiltrating endometriosis with fibromuscular tissue), and the potentially serious idiosyncratic toxicities of mTOR inhibitors that can be difficult to justify in young women with a chronic benign condition. This paper is centrally about endometriosis — it is a Letter to the Editor discussing the evidence and limitations of mTOR inhibitors (particularly everolimus) for endometriosis treatment.

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Abstract

Comment on: Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat StudyGeburtshilfe Frauenheilkd 2017; 77(01): 66-72DOI: 10.1055/s-0042-115566
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Bibliography

DOI https://doi.org/10.1055/s-0043-124518 Geburtsh Frauenheilk 2018; 78: 283 –284 © Georg Thieme Verlag KG Stuttgart · New York | ISSN 0016 ‑5751 Correspondence Simone Ferrero, MD, PhD Academic Unit of Obstetrics and Gynecology, Ospedale Policlinico San Martino Largo R. Benzi 10, 16132 Genoa, Italy [email protected] GebFra Science | Letter to the Editor 283Barra F and Ferrero S. mTor Inhibitors for … Geburtsh Frauenheilk 2018; 78: 283 –284 may be tolerable in oncological therapy, where the primary end- points are disease-free survival and overall survival, but it appears difficult to accept them in young women with endometriosis where the goal is improving the quality of life. In fact, endome- triosis is a chronic benign disease that requires a long-term ther- apy combining clinical efficacy (preventing recurrence, control- ling pain symptoms) with acceptable costs and toxicity. Given this background, it seems unlikely that everolimus may have a relevant role in the future treatment of women with endometriosis. Conflict of Interest The authors declare that they have no conflict of interest.

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 mod- ulators 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 phosphoryl- ation 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 mor- tality with everolimus in cancer patients. Oncologist 2014; 19: 661 –668 [7] Gajate P , Alonso-Gordoa T, Martinez-Saez O et al. Prognostic and predic- tive role of the PI3K ‑AKT-mTOR pathway in neuroendocrine neoplasms. Clin Transl Oncol 2017. doi:10.1007/s12094-017-1758-3 [8] Pallet N, Legendre C. Adverse events associated with mTOR inhibitors. Expert Opin Drug Saf 2013; 12: 177 –186 284 Barra F and Ferrero S. mTor Inhibitors for … Geburtsh Frauenheilk 2018; 78: 283 –284 GebFra Science | Letter to the Editor

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Condition tags

endometriosis

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References (8)

Cited by (8)

SciLite annotations

organisms 2
rodents rattus sp.
chemicals 4
temsirolimus everolimus everolimus everolimus

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