肿瘤细胞对化疗药物的耐受是肿瘤临床治疗的难题。肿瘤细胞耐药机理复杂，需要不断拓展新思路、整合生命科学新技术逐步加以阐明。近年来伴随“氧化应激与肿瘤耐药”之间关系的再认识，为阐明肿瘤耐药的分子机理、寻找新型药物靶标提供了创新“切入点”。本项目拟以临床常见肿瘤耐药细胞为模型，采用高通量氧化还原蛋白质组学技术建立肿瘤耐药相关的氧化还原蛋白组（Redoxome），筛选与鉴定一批肿瘤耐药相关的氧化还原蛋白（Redox sensor）。结合分子细胞学技术和实验动物模型阐明氧化还原蛋白在肿瘤耐药中的生物学功能及其信号调控网络。通过本项目的实施，预期建立肿瘤耐药相关的氧化还原蛋白数据库，筛选一批耐药相关的氧化还原蛋白，系统阐明3-5个关键氧化还原蛋白的生物学功能，明确耐药相关氧化还原蛋白或其信号网络中关键效应分子作为药物靶标在肿瘤耐药逆转或抗肿瘤药物增敏中的潜在应用价值。

Drug resistance is a major problem in cancer chemotherapy but the underlying mechanisms remain poorly defined. Understanding the mechanism of chemoresistance would allow development of novel anticancer drugs. To achieve this, innovative methods in combination with breakthrough technologies are needed. Recent studies of the relationship between oxidative stress and tumor drug resistance allowed us to gain insight into the molecular mechanism behind tumor drug resistance and thus would aid in discovery of novel drug targets. In the current study, we propose to use high-throughput Redox Proteomics strategies to build a tumor resistance- associated Redoxome, screening and identification of a number of tumor resistance-associated redox reguatory proteins (Redox sensors). Using a combination of molecular cell biology techniques and in vivo studies, we are interested to elucidate the biological functions of redox sensors and interrogate the redox signaling network in the context of tumor drug resistance. Upon successful implementation of this proposed project, a database of tumor drug resistance-related redoxomes will be established, and the biological functions of up to five typical redox sensors and their signaling network will be comprehensively characterized. Our goal is to identify those redox sensors,which hold the potential to serve as therapeutic targets to reverse drug resistance or improve drug sensitivity for clinic treatment with drug resistant patients.