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Cancer is a highly heterogeneous disease of the dysproliferating cells,suffering from extensive genomic and epigenomic defects.DNA methylation is the best characterized epigenetic mechanism,ensuring for the lasting transcription memory maintained across the cell divisions.The aberrant DNA methylation dictates the cancer-state specific changes of transcription and therefore phenotype and is a promising molecular target for cancer diagnosis.Chemo-resistance prevents curative chemotherapy of cancer.The focus of our research to develop and clinical use of the robust DNA methylation diagnostics to detect early,guide the personalize chemotherapy and the novel robust therapeutics (a,optimized tri-drug regimen and b,a broad anti-cancer oncolytic adenoviral therapeutics.) In this talk,I will use our studies in bladder cancer as a paradigm to demonstrate the robustness and promise of both approaches of ours and the discoveries for the precision management of cancer.