title: Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer.
abstract: Epithelial ovarian cancer is a major problem as about 75% of patients develop recurrence after initial primary treatment and tumors are often chemoresistant. This article reviews the role of the interleukin-6 (IL-6) in chemoresistance and suppression of tumor immunity in ovarian cancer and provides the rationale for modulating the IL-6/ IL-6 receptor (IL-6R) induced pathway as a potential new target for the treatment of ovarian cancer. IL-6 is elevated in serum and ascites of ovarian cancer patients and increased IL-6 levels correlate with chemoresistance and poor prognosis in these patients. IL-6 induced Jak/Stat3, Ras/MEK/ERK and PI3K/Ras signaling pathways lead to cell survival, proliferation, angiogenesis, and confers resistance to apoptosis induced by conventional therapies. Furthermore, IL-6 induces tumor-promoting macrophages which are known to foster tumor growth and suppress local immunity. However, direct proof of the clinical impact of IL-6 blocking on disease progression is missing necessiting further studies in which the IL-6(R) pathway is modulated and its clinical impact on (epithelial) ovarian cancer is tested.
authors.affiliation: Department of Clinical Oncology, Building 1, K1-P, Leiden University Medical Center, PO box 9600, 2300 RC Leiden, The Netherlands. e.m.dijkgraaf@lumc.nl
authors.forename: Eveline M
authors.initials: EM
authors.lastname: Dijkgraaf
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6