Abstract
Ovarian cancer (OC) is a life-threatening disease with high morbidity and mortality rates among women. Treatment inevitably requires the use of multiple drugs, including platinum-based agents, taxanes, and targeted therapies, across all stages and subtypes. However, multidrug resistance frequently develops, resulting in poor prognosis and recurrence. Exploring the mechanisms of this resistance and identifying methods to restore drug sensitivity have become urgent. Current research indicates that the Hedgehog (Hh) signaling pathway is associated with the development of tumor stemness and is closely linked to the emergence of multidrug resistance in OC. However, the specific mechanisms by which Hh signaling contributes to multidrug resistance and how this pathway can be effectively targeted to restore drug sensitivity remain insufficiently understood. This article systematically summarizes the major forms of drug resistance in OC and elucidates the roles and mechanisms of the Hh pathway in multidrug resistance. These include cell stemness, spheroid formation, tumor microenvironment changes, drug efflux and metabolism, DNA damage repair, and epithelial-mesenchymal transition. Additionally, the changes in multidrug resistance-related signaling pathways caused by Hh were reviewed. Finally, we discussed strategies to sensitize OC by targeting the Hh pathway in combination with chemotherapy or targeted drugs. This approach represents a promising strategy to overcome multidrug resistance in OC.