Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer

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Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer

Coward, Jermaine (author)

Kulbe, Hagen (author)

Chakravarty, Probir (author)

Leader, David (author)

Vassileva, Vessela (author)

Leinster, D. Andrew (author)

Thompson, Richard (author)

Schioppa, Tiziana (author)

Nemeth, Jeffery (author)

Vermeulen, Jessica (author)

Singh, Naveena (author)

Avril, Norbert (author)

Cummings, Jeff (author)

Rexhepaj, Elton (author)

Jirström, Karin (author): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Gallagher, William M. (author)

Brennan, Donal J. (author)

McNeish, Iain A. (author)

Balkwill, Frances R. (author)

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(creator_code:org_t)

2011
2011
English.
In: Clinical Cancer Research. - 1078-0432. ; 17:18, s. 6083-6096

Related links:: http://dx.doi.org/10...; show more...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Purpose: We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. Experimental Design: We combined preclinical and in silico experiments with a phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer. Results: Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases showed that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, while seven others had periods of disease stabilization. In patients treated for 6 months, there was a significant decline in plasma levels of IL-6-regulated CCL2, CXCL12, and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies. Conclusion: IL-6 stimulates inflammatory cytokine production, tumor angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and clinical studies. Clin Cancer Res; 17(18); 6083-96. (C) 2011 AACR.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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By the university: Lund University

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