The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?

The nuclear factor of kappa beta (NF-kappaB) transcription factor regulates the transcription of numerous genes including that of interleukin 6 (IL-6). The IL-6 acts as an autocrine and paracrine growth factor of androgen-independent prostate cancer. An aberrant expression of the IL-6 gene and an increase in IL-6 expression are detected in bone metastatic and hormone-refractory prostate cancer. IL-6 has been suggested to have a crucial role in the resistance to chemotherapy or hormonal therapy involving apoptotic cell death. The NF-kappaB/IL-6 dependent pathways promote tumour-cell survival and in most situations protect cells against apoptotic stimuli. These data provide a rational framework for targeting NF-kappaB and IL-6 activity in novel biologically based therapies for aggressive and androgen independent prostate cancers.