Mukherjee A, et al. - Whether targeting the chromatin-associated High Mobility Group Box 3 (HMGB3) protein can restore cisplatin sensitivity in cisplatin-resistant ovarian cancer cells, was investigated. Researchers found that cisplatin-sensitive and cisplatin-resistant cells showed HMGB3 depletion that caused transcriptional downregulation of the kinases ATR and CHK1, which resulted in attenuation of the ATR/CHK1/p-CHK1 DNA damage signaling pathway. A novel role for HMGB3 in transcriptional regulation was indicated by the observed link between HMGB3 and the promoter regions of ATR and CHK1. In cisplatin-resistant A2780/CP70 cells, a significantly increased apoptosis due to HMGB3 depletion was seen after cisplatin treatment. Overall, increased tumor cell sensitivity to platinum drugs in ovarian cancer can be achieved by targeted depletion of HMGB3 which leads to a reduction of cisplatin resistance in human ovarian cancer cells.