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

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.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation

“…In recent years, a multitude of strategies have been employed to eradicate tumor cells within ovarian tissue [ 97 , 240 , 241 ], the light-dependent nature of PDT suggests its potential safety superiority over other methods. Even if the photosensitizing agent remains in the body after transplantation, PDT is not toxic to the organism.…”

Implementation of ovarian tissue cryopreservation in Hong Kong

“…Ovarian autotransplantation is performed when a patient has fully recovered from disease, but this approach may carry a small risk of reintroducing malignant cells in patients with cancer. 42 The results of some studies have suggested that the risk of reintroducing malignant cells could be minimised by meticulous examination of representative biopsy samples via histology, immunohistochemistry, and molecular biology techniques. 43 Moreover, optical coherence tomography can be used to assess malignant cells in thawed ovarian tissue before transplantation.…”