title: Redefining the origin and evolution of ovarian cancer: a hormonal connection.
abstract: Ovarian cancer has the highest mortality of all female reproductive cancers. Late diagnosis, tumour heterogeneity and the development of chemoresistance contribute to this statistic and work against patient survival. Current studies have revealed novel concepts that impact our view on how ovarian cancer develops. The greatest impact is on our understanding that, as a disease, ovarian cancer has multiple cellular origins and that these malignant precursors are mostly derived from outside of the ovaries. In this review, we propose a new concept of a step-wise developmental process that may underwrite ovarian tumorigenesis and progression: (1) migration/recruitment to the ovaries; (2) seeding and establishment in the ovaries; (3) induction of a dormant cancer stage; and (4) expansion and tumor progression. We will discuss the relationship of each step with the changing ovarian function and milieu during the reproductive age and the subsequent occurrence of menopause. The realization that ovarian cancer development and progression occurs in distinct steps is critical for the search of adequate markers for early detection that will offer personalized strategies for prevention and therapy.
authors.affiliation: Department of ObstetricsGynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cardenas
authors.affiliation: Department of ObstetricsGynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Ayesha B
authors.initials: AB
authors.lastname: Alvero
authors.affiliation: Department of Obstetrics and GynecologyCHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors.forename: Bo Seong
authors.initials: BS
authors.lastname: Yun
authors.affiliation: Department of ObstetricsGynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA gil.mor@yale.edu.
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000473:pathology; D009367:Neoplasm Staging; D009852:Omentum / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D006062:Gonadotropins
keywords: gonadotrophin hypothesis; menopause; ovarian cancer; ovulation