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Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer
Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK
* Author to whom correspondence should be addressed.
Received: 9 May 2013; in revised form: 3 July 2013 / Accepted: 29 July 2013 / Published: 6 August 2013
(This article belongs to the Special Issue Chemokines
Abstract: It is well established that chronic inflammation underpins the development of a number of human cancers, with pro-inflammatory signaling within the tumor microenvironment contributing to tumor progression and metastasis. CXCL8 is an ELR+ pro-inflammatory CXC-chemokine which mediates its effects via signaling through two G protein-coupled receptors, CXCR1 and CXCR2. Elevated CXCL8-CXCR1/2 signaling within the tumor microenvironment of numerous cancers is known to enhance tumor progression via activation of signaling pathways promoting proliferation, angiogenesis, migration, invasion and cell survival. This review provides an overview of established roles of CXCL8-CXCR1/2 signaling in cancer and subsequently, discusses the possible strategies of targeting CXCL8-CXCR1/2 signaling in cancer, covering indirect strategies (e.g., anti-inflammatories, NFκB inhibitors) and direct CXCL8 or CXCR1/2 inhibition (e.g., neutralizing antibodies, small molecule receptor antagonists, pepducin inhibitors and siRNA strategies). Reports of pre-clinical cancer studies and clinical trials using CXCL8-CXCR1/2-targeting strategies for the treatment of inflammatory diseases will be discussed. The future translational opportunities for use of such agents in oncology will be discussed, with emphasis on exploitation in stratified populations.
Keywords: cancer; inflammation; cxcl8; cxcr1; cxcr2; chemokine-targeted therapy
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Campbell, L.M.; Maxwell, P.J.; Waugh, D.J. Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer. Pharmaceuticals 2013, 6, 929-959.
Campbell LM, Maxwell PJ, Waugh DJ. Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer. Pharmaceuticals. 2013; 6(8):929-959.
Campbell, Laura M.; Maxwell, Pamela J.; Waugh, David J. 2013. "Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer." Pharmaceuticals 6, no. 8: 929-959.