Next-generation sequencing unlocking precision medicine in ovarian cancer

Ovarian cancer (OC) is one of the most lethal malignancies, primarily due to late-stage diagnosis, biological heterogeneity, and high rates of recurrence. Advances in precision oncology have underscored the importance of molecular testing to improve risk stratification, guide targeted therapies and prognostic assessment. Next-generation sequencing (NGS) has emerged as a revolutionary technology that has made multi-gene analysis of various specimens, such as tumor tissue and liquid biopsies possible. NGS has become an integral part of OC management as it has a crucial role in the identification of genetic and somatic mutations. However, several factors, such as variability in test strategies, specimen selection, analysis time, and clinical applications hinder its consistent use in clinical settings. This review highlights existing evidence regarding the clinical utility of NGS-based molecular testing in OC, encompassing its uses in diagnosis, treatment stratification, disease monitoring and evaluation of hereditary risk. It addresses the molecular complexity of various histological subtypes, with a focus on the important genomic alterations, such as homologous recombination repair defect and BRCA1/2 pathogenic variants. The strengths and limitations of various bio-specimens are discussed in relation to their performance and clinical applicability. It also discusses the most appropriate timings and accessible methodologies of molecular testing, ranging from traditional to high-throughput NGS systems. The main obstacles to large-scale deployment, as well as the new models of integration, are outlined with the focus on the new role of the artificial intelligence-led decision support system.