title: Notch signaling in serous ovarian cancer.
abstract: Ovarian cancer is the most lethal of all gynecologic malignancies because women commonly present with advanced stage disease and develop chemotherapy refractory tumors. While cytoreductive surgery followed by platinum based chemotherapy are initially effective, ovarian tumors have a high propensity to recur highlighting the distinct need for novel therapeutics to improve outcomes for affected women. The Notch signaling pathway plays an established role in embryologic development and deregulation of this signaling cascade has been linked to many cancers. Recent genomic profiling of serous ovarian carcinoma revealed that Notch pathway alterations are among the most prevalent detected genomic changes. A growing body of scientific literature has confirmed heightened Notch signaling activity in ovarian carcinoma, and has utilized in vitro and in vivo models to suggest that targeting this pathway with gamma secretase inhibitors (GSIs) leads to anti-tumor effects. While it is currently unknown if Notch pathway inhibition can offer clinical benefit to women with ovarian cancer, several GSIs are currently in phase I and II trials across many disease sites including ovary. This review will provide background on Notch pathway function and will focus on the pre-clinical literature that links altered Notch signaling to ovarian cancer progression.
authors.affiliation: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. groeneweg.jolijn@gmail.com.|Harvard Medical School, Boston, MA, USA. groeneweg.jolijn@gmail.com.
authors.forename: Jolijn W
authors.initials: JW
authors.lastname: Groeneweg
authors.affiliation: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. rfoster1@MGH.Harvard.edu.|Harvard Medical School, Boston, MA, USA. rfoster1@MGH.Harvard.edu.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. rfoster1@MGH.Harvard.edu.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Foster
authors.affiliation: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. wgrowdon@MGH.Harvard.edu.|Harvard Medical School, Boston, MA, USA. wgrowdon@MGH.Harvard.edu.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. wgrowdon@MGH.Harvard.edu.
authors.forename: Whitfield B
authors.initials: WB
authors.lastname: Growdon
authors.affiliation: Division of Woman and Baby, Department of Gynecologic Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. R.Verheijen@umcutrecht.nl.
authors.forename: René H M
authors.initials: RH
authors.lastname: Verheijen
authors.affiliation: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. brueda@MGH.Harvard.edu.|Harvard Medical School, Boston, MA, USA. brueda@MGH.Harvard.edu.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. brueda@MGH.Harvard.edu.
authors.forename: Bo R
authors.initials: BR
authors.lastname: Rueda
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D051880:Receptors, Notch