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分子生物标志物与诊断杂志

Putative Surrogate Biomarkers to Predict Patients with Acquired Platinum Resistance in Ovarian Cancer

Abstract

Mu Wang, Dawn P G Brown, Jinsam You and Kerry G Bemis

Over 15,000 women die from ovarian cancer and there are approximately 23,000 new cases diagnosed each year. Platinum-based chemotherapy is still the primary treatment for ovarian cancer. Most patients with the disease are initially responsive to chemotherapeutic treatment. However, a majority of ovarian cancer patients eventually relapse and become refractory to additional treatment. This drug-resistance is a major impediment to the successful treatment of ovarian cancer. To date the mechanisms of drug-resistance remain poorly understood. Previous studies have suggested that many proteins, such as BRCA1, BRCA2, MDR1, MRP1, MDM2, hMLH1, HSP27, and HSP70, are differentially expressed in drug-resistant ovarian tumor cells by mRNA differential display analysis. However, biomarkers that can be used to differentiate chemotherapy responders from non-responders have not yet been developed. With recent developments in proteomic technologies, differential protein expression in complex biological samples can be analyzed. In this cell model based study, we applied a label-free protein quantification technology to discover potential protein biomarker candidates that can differentiate chemo-drug responders from non-responders. This experimental approach could also serve as a model tool for further clinical validation and biomarker development for other diseases.

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