Eveline M. Dijkgraaf, Marij J.P. Welters, Johan W.R. Nortier, Sjoerd H. van der Burg and Judith R. Kroep Pages 3816 - 3827 ( 12 )
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.
Ovarian cancer, interleukin-6, immunotherapy, Stat3, chemoresistance, tumor immunity, serum, ascites, cell survival, angiogenesis.
Department of Clinical Oncology, Building 1, K1-P, Leiden University Medical Center, PO box 9600, 2300 RC Leiden, The Netherlands.