Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. The interactions of cancer and stromal cells within the tumour microenvironment further affects disease evolution and response to therapy. In past decades, researchers have characterized the cellular, molecular, microenvironmental and immunological heterogeneity of ovarian carcinoma. Traditional treatment approaches have considered ovarian carcinoma as a single entity. This landscape is slowly changing with the increasing appreciation of heterogeneity and the recognition that delivering ineffective therapies can delay the development of effective personalized approaches as well as potentially change the molecular and cellular characteristics of the tumour, which might lead to additional resistance to subsequent therapy. In this Review we discuss the heterogeneity of ovarian carcinoma, outline the current treatment landscape for this malignancy and highlight potentially effective therapeutic strategies in development.
Ovarian carcinoma is characterized by a high degree of interpatient, intrapatient and intratumour heterogeneity, which poses therapeutic challenges because this disease cannot be considered as a single entity.
A better understanding of the extra-ovarian origins of precursor lesions can help with early detection and prevention of ovarian carcinoma.
Primary debulking surgery helps to reduce tumour burden and control tumours that are resistant to chemotherapy.
Maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors after a response to platinum-based chemotherapy in both first-line and second-line settings has prolonged the interval between response and disease relapse.
The integration of assessments of patient-reported outcomes in routine cancer treatment improves management.
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The authors thank W. Xu and D. Sharma (University of Toronto) for their invaluable contributions to the development of the Circos plots.
A.M. has received honoraria from AstraZeneca, Clovis, GSK and PharmaMar. A.M.O. is a principal investigator and participates in steering committees of trials sponsored by AstraZeneca, Clovis (without compensation) and GSK, and is the CEO of Ozmosis Research (without compensation). The other authors declare no competing interests.
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Veneziani, A.C., Gonzalez-Ochoa, E., Alqaisi, H. et al. Heterogeneity and treatment landscape of ovarian carcinoma. Nat Rev Clin Oncol 20, 820–842 (2023). https://doi.org/10.1038/s41571-023-00819-1