Prognostic significance and therapeutic potential of pyroptosis in gynecological malignancies

Gynecologic malignancies (GMs) impose a significant global health burden, ranking among the most common cancers in women and remaining a leading cause of cancer-related death [1,2]. Despite advances in surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, survival gains have been modest, and outcomes for recurrent or metastatic disease remain poor [2]. Ovarian cancer (OC), for instance, is often diagnosed at advanced stages due to the absence of specific symptoms, and its 5-year relative survival rate remains only 43–51%, much lower than that of breast cancer and other female malignancies [3,4]. Although cervical cancer (CC) incidence has decreased with screening and HPV vaccination, rising adenocarcinoma rates and an immunosuppressive tumor microenvironment (TME) have slowed mortality reduction [5,6]. Endometrial cancer (EC) is now the most common gynecologic malignancy in high-income countries, with incidence increasing alongside obesity, aging, and reproductive changes. It is the only major cancer with declining survival over the past four decades and shows marked racial disparities [7,8]. Beyond survival, patients frequently face treatment-related toxicities, reduced quality of life, and reproductive health challenges [9,10]. Novel approaches such as liquid biopsy, immunotherapy, and antibody–drug conjugates show promise in early detection, recurrence monitoring, and precision treatment [[11], [12], [13], [14]]. However, resistance, limited durability of benefit, and barriers to clinical translation remain unresolved. Taken together, GMs present persistent challenges across the continuum of care, highlighting the need to identify novel molecular mechanisms, refine risk stratification, and develop innovative therapies to improve long-term outcomes.