最新研究表明肿瘤对化疗和放疗的敏感性取决于DNA损伤应答反应（DDR），DNA损伤反应中细胞周期调控，DNA修复和凋亡决定了对上述治疗的敏感还是耐受。而不同分化状态的细胞和不同组织来源的细胞对于DNA损伤导致的DDR存在着显著差异。耐药是肿瘤干细胞的重要特征。但肿瘤干细胞与DDR相关的耐药机制并不清楚。我们前期运用侧群细胞，顺铂耐药富集，和CD44分选等策略证实了膀胱癌中存在着肿瘤干细胞，具有干性和耐药的特征，并发现与DDR相关基因组群中XPC和Chk2过度表达，提示它们在膀胱癌干细胞顺铂介导的DNA损伤的DDR中可能起关键作用。由于XPC是DNA损伤最早的识别蛋白。除了经典的DNA修复作用，它在DDR中可能参与DDR的核心checkpiont调控作用，表现出膀胱肿瘤干细胞有别于已分化细胞的DDR特征。探明上述可能的分子机制从崭新的角度对于理解膀胱癌的耐药具有重要理论意义和潜在的应用价值。

The drug or radiation resistant are rely on the DNA damage response (DDR).The DDR (cell cycle checkpiont,DNA repair and apoptosis ) decides the fate of cell upon the DNA damage.The DDR are varied among diferent tissue-oringed and cell statue (stem cell or diferented cell).The drug-resistant is the hallmark of cancer stem cell,but little was known about mechanism related DDR in the cancer stem cell.Previously we confirmed and identified the cancer stem cells in human bladder cancer and found the overexpression of XPC and Chk2 in DDR related gene set. This noval finding hints that XPC is involve in the checkpoint regulation as an important initial factor upon the cisplatin-mediated DNA damage response beside to playing a role in nucleotide excision repair(NER) pathway. The molecular mechanism will be investigated how over expression of XPC lead to the distingished DDR in bladder cancer stem cell from non cancer stem cell in the project. This project will provide new insight into understand molecular mechanism of chemotherapy resistant in human bladder and new potential molecular target for cancer therapy.