title: PI3K pathway in gynecologic malignancies.
abstract: Alterations in PI3K signaling are common in gynecologic malignancies. Alterations detected vary with gynecologic cancer type, histologic subtypes within these, and clinical phenotypes. The distinction into type I and type II endometrial and ovarian carcinomas is reflected in distribution of changes detected in several of the PI3K members. PIK3CA mutations and amplifications are common in endometrial, ovarian, and cervical cancers. PTEN mutations and deletions are frequent in endometrial cancers. Several immunohistochemical studies of protein expression have explored these and other potential surrogate markers for PI3K pathway activation. Biomarkers to measure level of PI3K activity in clinical samples are not established. Whether amplifications, mutations, and deletions of the PI3K pathway members, and in particular change in their expression levels, result in clinically relevant pathway activation needs to be further explored. Also, to what extent these alterations drive the tumor behavior and are critical targets for therapeutics to improve patient survival needs to be further tested to establish predictive biomarkers for response to PI3K inhibition.
authors.affiliation: From the Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Institute of Clinical Sciences, University of Bergen, Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Henrica Maria
authors.initials: HM
authors.lastname: Werner
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005833:Genital Neoplasms, Female / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase