Mechanism of chemoresistance by HDAC1-associating protein and development of molecular targeted therapy

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Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. Using an in vitro model, we previously found that the RET finger protein (RFP) which is known as HDAC-associating protein, confers cancer cell resistance to anticancer drugs. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Depletion of RFP by RNA interference in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a candidate for a molecular-targeted agent.