Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway.

Ronald Peek,Lotte L Eijkenboom,Didi D M Braat,Catharina C M Beerendonk

doi:10.3390/jcm10194362

Ronald Peek, Lotte L Eijkenboom + Show 2 more

Open Access

https://doi.org/10.3390/jcm10194362

Copy DOI

Abstract

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

Highlights

Autotransplantation of cryopreserved ovarian cortex fragments has become a viable option for the restoration of fertility in women suffering from loss of reproductive potential
The technique is based on the cryopreservation of ovarian cortex tissue fragments (OTC) containing primordial follicles that are capable of restoring fertility after grafting
We have shown the successful purging of ovarian tissue harboring tumor foci from rhabdomyosarcoma by short-term pharmacological inhibition of YAP/TAZ oncoproteins with Verteporfin, without compromising ovarian tissue integrity [16]

Summary

Introduction

Autotransplantation of cryopreserved ovarian cortex fragments has become a viable option for the restoration of fertility in women suffering from loss of reproductive potential. The technique is based on the cryopreservation of ovarian cortex tissue fragments (OTC) containing primordial follicles that are capable of restoring fertility after grafting. Despite its broad applicability and high success rate, the autologous transplantation of ovarian tissue in cancer patients is not without concern. In most of these patients the ovarian tissue is harvested prior to chemotherapy leaving the potential risk of reintroducing malignancy via cancer cells present in the graft during autotransplantation. The risk of disease transmission through grafting was reported to be relatively small [1,2]

Objectives

Methods

Results

Conclusion