Cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy is the gold standard for muscle invasive bladder cancer (MIBC) due to an overall survival benefit with NAC. The greatest benefit is seen in patients with a complete response, however such a response fails to occur in 40% of patients. These patients are therefore subjected to treatment morbidity and possibly a delay to surgery. There is urgent need to develop markers to identify patients who will respond to NAC treatment. In a preliminary study we identified differential DNA methylation patterns in a small group of patients who had exhibited either response or resistance to NAC.

In this study we aim to: 1) monitor bladder cancer specific DNA methylation markers in MIBC patients’ urine sediment to predict response to NAC treatment before cystectomy. We will collect 60 patients’ urine sediments during NAC treatment; 2) identify DNA methylation markers that predict response to NAC in MIBC and validate the marker panel generated in Aim 1 and TCGA database based on patients’ clinic outcome. We expect that through this proposal, we will develop robust biomarker panels capable of predicting response versus resistance to NAC. These markers would represent non-invasive methods to determine which MIBC patients will benefit from NAC, and they have the potential to provide targets for novel therapies in those with resistance.

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