LAUSR

Significance Ovarian cancer is the most lethal gynecological cancer. Clinically approved chemotherapies aim to slow or stop tumor growth; however, cancer cells continue to evolve between chemotherapy cycles, acquiring properties that allow cell survival and successful dissemination, subsequently developing into life-threatening metastatic tumors. There is an urgent need to develop more effective therapeutic strategies based on the biology of disseminated and metastatic ovarian tumors to achieve long-term remission. Here, we leveraged tumor-associated overactive membrane-anchored serine proteases to develop a potent therapeutic agent that selectively kills ovarian tumor cells by inactivation of pathways that promote tumor cell survival. Clinical translation of these preclinical findings could be an effective therapeutic strategy to improve the prognosis for women with late-stage ovarian cancer.