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.
Current Pharmaceutical Design
Title:Interleukin-6/interleukin-6 Receptor Pathway as a New Therapy Target in Epithelial Ovarian Cancer
Volume: 18 Issue: 25
Author(s): Eveline M. Dijkgraaf, Marij J.P. Welters, Johan W.R. Nortier, Sjoerd H. van der Burg and Judith R. Kroep
Affiliation:
Keywords: Ovarian cancer, interleukin-6, immunotherapy, Stat3, chemoresistance, tumor immunity, serum, ascites, cell survival, angiogenesis.
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.
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Cite this article as:
M. Dijkgraaf Eveline, J.P. Welters Marij, W.R. Nortier Johan, H. van der Burg Sjoerd and R. Kroep Judith, Interleukin-6/interleukin-6 Receptor Pathway as a New Therapy Target in Epithelial Ovarian Cancer, Current Pharmaceutical Design 2012; 18 (25) . https://dx.doi.org/10.2174/138161212802002797
DOI https://dx.doi.org/10.2174/138161212802002797 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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