Evaluation of the alkaline comet assay as a predictive test of invasive bladder cancer treatment : prediction of bladder cancer cell radiosensitivity and chemosensitivity
thesisposted on 15.12.2014, 10:30 by Manar Moneef. Al-Moneef
This thesis investigates the alkaline comet assay (ACA) as a potentially rapid, prognostic test in the treatment of muscle invasive bladder cancer. In the UK, the two main treatment options for invasive bladder cancer are radiotherapy (RT) or cystectomy. However, -50% of patients undergoing RT fail to respond, and these patients are disadvantaged by the absence of predictive information regarding their tumour's radiosensitivity. Furthermore, in the continuing search for effective local control with improved survival, chemotherapeutic agents have been used in conjunction with RT and cystectomy. However, in the treatment of some patients, local control is achieved without the use of cytotoxic chemotherapy and as such these patients do not benefit from this additional treatment. If tumour cell radiosensitivity and chemosensitivity could be predicted in advance, it may be possible to improve control rates by selecting patients for the most appropriate treatment. In the present study we are evaluating ACA as a rapid predictive measure of bladder cancer cell radiosensitivity and chemosensitivity. Using a panel of six human bladder cancer cell lines of differing radio- and chemosensitivities, the relationship of cell survival and viability to the formation and repair of both radiogenic and chemotherapeutic drug-induced DNA damage, as determined by ACA, was assessed. For all the cell lines studied the ACA measures of initial DNA damage formation correlate with cell killing/loss of cell viability, with a greater comet response/damage level being noted in the sensitive cells. Measures of repair, also correlate with cell survival and viability, though to a lesser degree. Finally, in a preliminary study, epithelial cells isolated from human bladder cancer biopsies also reveal a range of radio-responses as determined by ACA, which is taken to reflect actual variation in tumour cell radiosensitivity. Overall, these studies demonstrate ACA to be a good predictor of bladder cancer cell radiosensitivity and chemosensitivity.