Targeting Microtubule-Associated Protein Tau in Chemotherapy-Resistant Models of High-Grade Serous Ovarian Carcinoma.

Relapsed, recurrent, chemotherapy-resistant high-grade serous ovarian carcinoma is the deadliest stage of this disease. Expression of microtubule-associated protein tau (tau) has been linked to resistance to paclitaxel treatment. Here, I used models of platinum-resistant and created models of platinum/paclitaxel-resistant high-grade serous ovarian carcinoma to examine the impact of reducing tau expression on cell survival and tumor burden in cell culture and xenograft and syngeneic models of the disease. Tau was overexpressed in platinum/paclitaxel-resistant models; expression of phosphoSer396 and phosphoThr181 species was also found. A treatment with leucomethylene blue reduced the levels of tau in treated cells, was cytotoxic in cell cultures, and efficiently reduced the tumor burden in xenograft models. Furthermore, a combination of leucomethylene blue and paclitaxel synergized in eliminating cancer cells in cell culture and xenograft models. These findings underscore the feasibility of targeting tau as a treatment option in terminal-stage high-grade serous ovarian cancer.