Bax, Sara Marie (2020) Inhibition of the Mammalian Target of Rapamycin (mTOR) in Mammary Residual Tumor Cells. thesis, Medicine.
Full text available on request.Abstract
Breast cancer is the leading cause of cancer mortality in women with a particularly poor prognosis in recurrences (1-3). Breast cancer recurrence is enhanced in obesity and it is proposed that the PI3K-Akt-mTOR pathway is involved (4-6). Recurrences are potentially driven by residual tumor cells (RTCs) and greater RTCs are found in obesity (7,8). Inhibition of the mTOR pathway by Everolimus in RTCs was therefore hypothesized to reduce the RTC burden in obesity. The study was done on immunocompetent TetO-NeuNT mono-transgenic mouse models with orthotopically injected 54074 mammary tumor cells with dietary induced obesity and lean controls. After the induced primary mammary tumor regressed to a nonpalpable state, the mice were treated with Everolimus or vehicle for six weeks. The local RTC burden was quantified with droplet digital PCR and mTOR pathway activity with immunofluorescence. A non-significant reduction of RTCs was seen in the Everolimus groups. While lean mice had little fewer RTCs compared to obese mice when treated with Everolimus, an obesity-associated increase in RTCs in absence of Everolimus was not seen and contrarily greater RTCs were found in lean mice. Since the absence of an obesityassociated increase in RTCs contrasted to earlier data and the mTOR pathway activity at a cellular level could not be quantified in this study, further validation experiments on the mTOR pathway activity and RTC burden in obesity are warranted. However, mTOR pathway inhibition by Everolimus seems associated with a reduced RTC burden, therefore potentially providing mTOR as a biological target for the treatment of RTCs.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Smit, Dr. W.M. and Chodosh, MD, Ph.D, L.A. |
| Faculty: | Medical Sciences |
| Date Deposited: | 11 Aug 2023 11:46 |
| Last Modified: | 11 Aug 2023 11:46 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3623 |
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