Molen, M.C. van der (2015) Docetaxel resistance in castration resistant prostate cancer :the role of c-Jun and the androgen receptor. thesis, Medicine.
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Abstract
Prostate cancer is the second most common malignancy in men and has remained the second leading cause of cancer related death worldwide. Metastatic castration resistant prostate cancer (mCRPC) is a lethal disease with a poor prognosis. Although new promising drugs in mCRPC treatment have been approved, the chemotherapeutic agent docetaxel has remained a cornerstone of the standard of care in men worldwide. However, only half of patients will repond to docetaxel therapy and most men will experience progression of the disease within the first year of treatment, resulting in resistance being the main limitation of its efficacy. A better understanding of the impact of docetaxel on prostate cancer cells could provide opportunities for preventing or delaying the development of resistance to docetaxel. Previous studies demonstrated that docetaxel increases the expression of androgen receptor and prostate specific antigene (PSA), but how these effects are mediated was yet unknown. In this report, PSA quantification tests and Western blot analyzes were performed to elucidate the role of proto-oncogene c-Jun and the androgen receptor in docetaxel resistance. It was shown that docetaxel treatment leads to an increased expression of the androgen receptor, which is independent of endogenous c-Jun levels and that the time dependent increase in PSA level is mediated by the androgen receptor. These results underline once more the importance of further research on the regulation of the androgen receptor, which plays an important role in both onset and progression of the disease.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Jong, Prof. I.J. de MD |
| Supervisor name: | Second supervisor: and Dizeyi, PhDAss. prof. N. / and Abrahamsson, Prof. P.A. MD and Clinical Research Center and Malmö, Sweden |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:57 |
| Last Modified: | 25 Jun 2020 10:57 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1773 |
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