Cell death-based treatment of ovarian cancer

Abstract Ovarian cancer (OC) is the seventh most prevalent type of cancer in women and one of the most lethal gynecological malignancies, due to the poor prognosis (with a 5-year survival rate of about 50%), the lack of specific clinical symptoms, the absence of effective screening, and the fact that the tumor grows without obvious signs. These factors complicate early detection, when clinical intervention is most effective, leading to late diagnosis. Standard treatment for OC includes cytoreductive surgery followed by platinum-based chemotherapy (PBC) with carboplatin and paclitaxel or their analogs. Conversely, despite the initial positive response to chemotherapy, many patients experience disease recurrence and develop chemotherapy resistance, which makes long-term treatment challenging and often results in fatal outcomes. Here, we focus on therapeutic strategies that overcome this resistance by precisely targeting pathways of programmed cell death (PCD), thereby opening new avenues for treatment. The potential of using PCD in OC treatment is being considered, focusing on key regulatory mechanisms: triggering intrinsic and/or extrinsic apoptosis; the complex role of autophagy in both promoting survival and inducing cell death; the emerging relevance of ferroptosis activation through inhibition of GPX4 or blockade of Xc- system; and the potential of using necroptosis and pyroptosis as immunogenic PCD modalities that can activate an immune response against the tumor. The use of these different PCD pathways offers opportunities to sensitize resistant tumors and improve patient outcomes.