Oncotarget

Interview with Dr. Tanwar from the School of Biomedical Sciences and Pharmacy

Oncotarget published " Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium " which reported that the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear.

mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis.

This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium.

These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, they analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls.

Collectively, the authors have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer.

Dr. Pradeep S. Tanwar from The School of Biomedical Sciences and Pharmacy in New South Wales Australia said, "Age is a major risk factor for the development of epithelial ovarian cancer. "

Age is a major risk factor for the development of epithelial ovarian cancer.

Interestingly, a higher number of inclusion cysts are observed in the contralateral ovaries of unilateral OvCa patients and in the ovaries of patients with hereditary predisposition to OvCa compared to the general population.

Assessment of genetic aberrations in ovaries of patients with OvCa, borderline tumours and non-neoplastic disease showed chromosomal alterations in OSE and inclusion cysts.

Moreover, a higher proportion of aneusomic cells were present in the inclusion cysts from OvCa and borderline tumour patients than controls, suggesting that these OSE-derived cysts have the potential to progress to OvCa.

Firstly, mice with germ cell deficiency also exhibit OSE hyperplasia and inclusion cysts, and develop ovarian epithelial tumours with advancing age.

Collectively, these findings suggest that age associated changes in ovary/OSE contribute to the formation of inclusion cysts and consequently, OvCa.

The Tanwar Research Team concluded in their Oncotarget Research Output, "our examination of aged human and mouse ovaries showed hyperactivation of mTOR signalling in OSE pathological lesions. Suppression of mTOR signalling inhibited the development of these lesions in the Ptentg and rapamycin treated mice. Treatment of human OvCa cells with mTOR inhibitors significantly decreased the growth and viability of these cells suggesting that targeting the mTOR pathway might be an effective therapeutic strategy for preventing OvCa. "

DOI - https://doi.org/10.18632/oncotarget.8468

Full text - https://www.oncotarget.com/article/8468/text/

Correspondence to - Pradeep S. Tanwar - pradeep.tanwar@newcastle.edu.au

Keywords - ovarian aging, rapamycin, mTOR, ovary, OSE, Gerotarget

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