IL-6/IL-6R as a potential key signaling pathway in prostate cancer development

Table 1 Summary of several studies on IL-6, sIL-6R and sgp130 levels in prostate cancer patients and targeted therapies for the IL-6 signaling pathway

Prognostic implications	Ref.	Conclusions
	[15,16]	L-6 level is a significant prognostic factor for PC. A significantly shorter survival in PC patients was associated with elevated IL-6 levels, serum PSA levels and aggressive disease
	[48,57-60]	The serum levels of IL-6 were significantly higher in PC patients with metastatic disease
	[48,62-66]	The levels of IL-6, sIL-6R and TGF-β1 predicted biochemical recurrence after surgery or radical prostatectomy
	[75]	In patients treated with radical prostatectomy higher preoperative plasma sgp130 was significantly associated with higher pathological Gleason, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and biochemical recurrence. The postoperative sgp130 levels were 18% lower than preoperative levels
Therapeutic implications	[131-133]	These studies involved the chimeric monoclonal anti-IL-6 antibody, siltuximab (CNT0 328) It was shown that tumor growth in nude mice inoculated with LNCaP-IL-6+ cells after CNTO 328 treatment was reduced. Analogous results were obtained when PC3 and LuCaP 35 xenografts were treated with CNTO 328
	[135]	The administration of siltuximab in a group of patients who had already received docetaxel therapy had no clinical efficacy
	[136]	PC cells can develop resistance to docetaxel and STAT1 is increasingly expressed in docetaxel-resistant PC cells
	[84]	The treatment of the PC3 cell line with Sant7 inhibits cell growth more efficiently than other anti-IL-6 antibodies
	[134]	CNT0 328 can inhibit PC cell growth in vitro and improve survival by reducing the level of cachexia in an animal model of PC
	[133]	In mice, CNT0 328 inhibited the conversion of CSPC into more aggressive disease
	[137]	STAT3 and MAPK activity is suppressed in patients taking siltuximab, which may inhibit IL-6-mediated drug resistance

PC: Prostate cancer; CSPC: Castration-sensitive prostate cancer; TGF-β1: Transforming growth factor-beta1; IL-6: Interleukin-6; sIL-6R: Soluble interleukin-6 receptor; STAT3: Signal transducer and activator of transcription 3; MAPK: Mitogen-activated protein kinase.