Interleukin-6/interleukin-6 Receptor Pathway as a New Therapy Target in Epithelial Ovarian Cancer

Author(s): Eveline M. Dijkgraaf, Marij J.P. Welters, Johan W.R. Nortier, Sjoerd H. van der Burg, Judith R. Kroep.

Journal Name: Current Pharmaceutical Design

Volume 18 , Issue 25 , 2012

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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.

Keywords: Ovarian cancer, interleukin-6, immunotherapy, Stat3, chemoresistance, tumor immunity, serum, ascites, cell survival, angiogenesis.

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Article Details

VOLUME: 18
ISSUE: 25
Year: 2012
Page: [3816 - 3827]
Pages: 12
DOI: 10.2174/138161212802002797
Price: $58

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