Ovarian Cancer: Epidemiology, Disease Mechanisms, New Diagnosis and Treatment Strategies, and Research Directions

ABSTRACT Ovarian cancer (OC) continues to be the deadliest gynecological malignancy and a significant cause of cancer‐related mortality among women worldwide. Standard treatment strategies typically entail platinum‐based chemotherapy in conjunction with cytoreductive surgery. Nevertheless, the efficacy of therapeutic interventions is frequently restricted by substantial drug resistance and treatment‐related toxicity, resulting in poor long‐term survival and high recurrence rates. The majority of OC cases are classified as epithelial ovarian cancer (EOC), which is an exceedingly heterogeneous condition. The molecular profiles, clinical outcomes, and treatment responses of the five major histological subtypes of EOC, high‐grade serous, low‐grade serous, clear cell, endometrioid, and mucinous differ significantly. Recent discoveries regarding the pathogenesis of high‐grade serous carcinoma (HGSC) indicate that a significant number of cases originate of precursor lesions in the fallopian tube fimbria. This paradigm shift has redefined the classification of OC and offered a promising preventive approach through opportunistic salpingectomy. Meanwhile, the global incidence patterns indicate a decrease in high‐income countries, which may be attributed to earlier detection and increased contraceptive use. Conversely, a rise in incidence is observed in low‐ and middle‐income settings, which is attributed to changes in reproductive behaviors and lifestyle factors. The early diagnosis, prognosis, and selection of targeted therapies depend on the screening and validation of reliable biomarkers, including CA‐125, HE4, BRCA1 and BRCA2 mutations, and homologous recombination deficiency (HRD) status. Many current biomarkers lack the specificity and sensitivity required for effective clinical decision‐making, despite ongoing advancements. This review offers a comprehensive examination of the epidemiology, molecular and histological subtypes, and evolving classification of OC. It critically evaluates the advancements in targeted therapy, highlights the significance of the tumor biomarkers in the development of precision medicine, and explores preventive strategies, including salpingectomy. Subsequently, it outlines the current challenges and future directions in the discovery of biomarkers and personalized treatment approaches, aiming to improve clinical outcomes and patient survival rates for this devastating disease.