title: Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer.
abstract: Genomic information is being used to develop robust prognostic and predictive biomarkers that will provide companion diagnostics for emerging molecular targeted therapies. The genetics and associated molecular pathways in ovarian cancer are increasingly being used for the development of novel targeted drugs with a much greater therapeutic specificity than standard chemotherapy. This review will provide an update on recent research on the therapeutic opportunities presented by mutational alterations to the epidermal growth factor receptor (EGFR) and phosphatidylinositide-3-kinase (PI3K/AKT/mTOR) pathways. In addition, the role of the deficient BRCA1/2-mediated homologous recombination (HR) ("BRCAness") pathway is presented. Understanding the molecular biology of these pathways in the context of contemporary drug development means that somatic mutations and epigenetic losses of BRCA1/2 and PTEN in ovarian cancer are being used to predict sensitivity to new poly(ADP-ribose) polymerase (PARP) inhibitors that exhibit synthetic lethality with BRCA1/2 dysfunction and other repair pathways. Future predictive "biomarker pipelines" are being developed so that ovarian cancer patients will be able to avoid having treatments with drugs that will have no effect, whereas other patients with cancer may be eligible for therapies with a much higher probability of treatment response.
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Johanne I
authors.initials: JI
authors.lastname: Weberpals
authors.forename: Madhuri
authors.initials: M
authors.lastname: Koti
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D004260:DNA Repair; D018450:Disease Progression; D057890:Epigenomics; D005260:Female; D042822:Genomic Instability; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents