title: Minireview: human ovarian cancer: biology, current management, and paths to personalizing therapy.
abstract: More than 90% of ovarian cancers have been thought to arise from epithelial cells that cover the ovarian surface or, more frequently, line subserosal cysts. Recent studies suggest that histologically similar cancers can arise from the fimbriae of Fallopian tubes and from deposits of endometriosis. Different histotypes are observed that resemble epithelial cells from the normal Fallopian tube (serous), endometrium (endometrioid), cervical glands (mucinous), and vaginal rests (clear cell) and that share expression of relevant HOX genes which drive normal gynecological differentiation. Two groups of epithelial ovarian cancers have been distinguished: type I low-grade cancers that present in early stage, grow slowly, and resist conventional chemotherapy but may respond to hormonal manipulation; and type II high-grade cancers that are generally diagnosed in advanced stage and grow aggressively but respond to chemotherapy. Type I cancers have wild-type p53 and BRCA1/2, but have frequent mutations of Ras and Raf as well as expression of IGFR and activation of the phosphatidylinositol-3-kinase (PI3K) pathway. Virtually all type II cancers have mutations of p53, and almost half have mutation or dysfunction of BRCA1/2, but other mutations are rare, and oncogenesis appears to be driven by amplification of several growth-regulatory genes that activate the Ras/MAPK and PI3K pathways. Cytoreductive surgery and combination chemotherapy with platinum compounds and taxanes have improved 5-yr survival, but less than 40% of all stages can be cured. Novel therapies are being developed that target high-grade serous cancer cells with PI3Kness or BRCAness as well as the tumor vasculature. Both in silico and animal models are needed that more closely resemble type I and type II cancers to facilitate the identification of novel targets and to predict response to combinations of new agents.
authors.affiliation: M.D. Anderson Cancer Center, Translational Research, Houston, Texas 77030, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Romero
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004195:Disease Models, Animal; D004358:Drug Therapy; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D057285:Precision Medicine / Q000639:trends*