title: Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk.
abstract: Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.
authors.affiliation: Unit of Endocrinology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lauretta
authors.affiliation: Unit of Endocrinology, Department of Systems' Medicine, University of Rome Tor Vergata, Section of Reproductive Endocrinology, Fatebenefratelli Hospital "San Giovanni Calibita" Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanzolla
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Department of Gynaecologic Oncology, HPV-Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Unit of Endocrinology, Department of Systems' Medicine, University of Rome Tor Vergata, Section of Reproductive Endocrinology, Fatebenefratelli Hospital "San Giovanni Calibita" Rome, Italy.
authors.forename: Costanzo
authors.initials: C
authors.lastname: Moretti
authors.affiliation: Unit of Endocrinology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marialuisa
authors.identifier: 0000-0002-2124-1335
authors.initials: M
authors.lastname: Appetecchia