title: [The molecular biology of epithelial ovarian cancer].
abstract: Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.
authors.affiliation: Institut Gustave-Roussy, département de médecine, comité pluridisciplinaire de gynécologie, 114, rue Édouard-Vaillant, 94800 Villejuif, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Leary
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Youssef
authors.initials: Y
authors.lastname: Tazi
authors.forename: Philippe
authors.initials: P
authors.lastname: Morice
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvillard
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gouy
authors.forename: Catherine
authors.initials: C
authors.lastname: Uzan
authors.forename: Hélène
authors.initials: H
authors.lastname: Gauthier
authors.forename: Corinne
authors.initials: C
authors.lastname: Balleyguier
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhommé
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods; D000077216:Carcinoma, Ovarian Epithelial; D004260:DNA Repair / Q000502:physiology; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D010053:Ovary / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D057170:Translational Research, Biomedical
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents