title: Interleukin-6: an angiogenic target in solid tumours.
abstract: During the past decade, incorporating anti-angiogenic agents into the therapeutic management of a myriad of malignancies has in certain cases made a significant impact on survival. However, the development of resistance to these drugs is inevitable and swift disease progression on their cessation often ensues. Hence, there is a drive to devise strategies that aim to enhance response to anti-angiogenic therapies by combining them with other targeted agents that facilitate evasion from resistance. The pleiotropic cytokine, interleukin-6 (IL-6), exerts pro-angiogenic effects in the tumour microenvironment of several solid malignancies and there is emerging evidence that reveals significant relationships between IL-6 signalling and treatment failure with antibodies directed against vascular endothelial growth factor (VEGF). This review summarises the role of IL-6 in pivotal angiogenic processes and preclinical/clinical research to support the future introduction of anti-IL-6 therapies to be utilised either in combination with other anti-angiogenic drugs or as a salvage therapy for patients with diseases that become refractory to these approaches.
authors.affiliation: Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Middleton
authors.affiliation: Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jones
authors.affiliation: Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia.
authors.forename: Zarnie
authors.initials: Z
authors.lastname: Lwin
authors.affiliation: Mater Adult Hospital, Department of Medical Oncology, Raymond Terrace, Brisbane, QLD 4101, Australia; Inflammation & Cancer Therapeutics Group, Mater Research, Level 4, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD 4102, Australia; School of Medicine, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. Electronic address: jcoward@mmri.mater.org.au.
authors.forename: Jermaine I G
authors.initials: JI
authors.lastname: Coward
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors
keywords: Angiogenesis; Bevacizumab; HIF-1α; IL-6; STAT3; Siltuximab; Sunitinib; VEGF