Interleukin-6: an angiogenic target in solid tumours

Crit Rev Oncol Hematol. 2014 Jan;89(1):129-39. doi: 10.1016/j.critrevonc.2013.08.004. Epub 2013 Aug 28.


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.

Keywords: Angiogenesis; Bevacizumab; HIF-1α; IL-6; STAT3; Siltuximab; Sunitinib; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Treatment Outcome


  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Interleukin-6