Early stage prostate cancer is highly manageable using definitive radical prostatectomy and/ or radiotherapy techniques. Unfortunately, for some men,transition to castrate-resistant prostate cancer is both inevitable and incurable with few life-extending therapies available. Therefore, there is an urgent need for novel agents to improve the oncological and survival outcomes for these last-resort patients.One such modality may be α1-adrenoceptor antagonists. Clinically, some of these drugs reportedly increase benign and cancerous prostatic apoptosis. In vitro studies indicate that this anticancer effect occurs via α1-adrenoceptor independent mechanisms. However, the cytotoxic profile of these drugs have yet to be fully characterised, including whether these agents may be useful in improving anticancer treatment efficacy. To address the gaps in literature, the relative cytotoxic potencies and underlying cell death mechanisms (apoptosis and autophagy) were determined for six α1-adrenoceptor antagonists on castrate-sensitive and castrate-resistant prostate cancer cells. This is the first report of radiosensitising effects of these drugs in prostate cancer cells, suggesting that these agents may have novel clinical benefits for patients undergoing radiotherapy. Likewise, the preliminarily findings of this thesis suggest that these drugs may be a novel alternative intravesical treatment option for bladder cancer and warrants further investigation.
Year Manuscript Completed
Hormones, Hormone Substitutes, and Hormone Antagonists | Oncology
Prostate Cancer Treatment; Prostatic Neoplasms; Adrenoceptor Antagonists.
Primary Language of Manuscript
Recommended CitationAmanda L. Forbes (2016) Quinazoline-based alpha1-adrenoceptor antagonists and prostate cancer., PhD, ePublications@bond, Faculty of Health Sciences and Medicine.
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