Interleukin-6 and prostate cancer: Current developments and unsolved questions

Mol Cell Endocrinol. 2018 Feb 15;462(Pt A):25-30. doi: 10.1016/j.mce.2017.03.012. Epub 2017 Mar 16.


Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models. Experimental therapies have been proposed in order to block the IL-6/STAT3 signaling pathway. In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance. However, clinically, the anti-IL-6 antibody was not successful as a monotherapy in phase II studies in patients with metastatic PCa. IL-6 is implicated in regulation of cellular stemness by increasing phosphorylation of STAT3. The cytokine has also a role in development of resistance to the non-steroidal anti-androgen enzalutamide. Endogenous inhibitors of IL-6 are suppressors of cytokine signaling and protein inhibitors of activated STAT. Although they inhibit signal transduction through STAT3, they may also exhibit anti-apoptotic effects. On the basis of complexity of IL-6 action in PCa, an individualized approach is needed to identify patients who will benefit from anti-IL-6 therapy in combination with standard treatments.

Keywords: Antibodies; Cancer progression; Interleukin-6; STAT3; Therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Interleukin-6 / metabolism*
  • Male
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prostatic Neoplasms / metabolism*
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism


  • Interleukin-6
  • Receptors, Androgen
  • Tumor Suppressor Proteins