Prostate cancer: leading and misleading routes to TRAIL of death

Abstract

Prostate cancer is a multifaceted disease that arises because of misrepresentation of linear and integrated signaling cascades that regulate gene network in normal and cancer cells. Programmed cell death is modulated by intracellular regulators within each cell and various lines of evidence suggest that there is under- expression and over-expression of pro-apoptotic and anti-apoptotic gene subsets respectively. Apoptosis is a response to the cellular microenvironment, and the cell microenvironment can be regulated by multiple signaling cascades at a higher organizational level by suppressing survival signals notably at genetic, epigenetic, transcriptional and post-transcriptional level. Unquestionably, drug-discovery approaches over the last decade aiming at neutralizing anti-apoptotic proteins, over-expressing pro-apoptotic proteins and enhancing the cell surface appearance of TRAIL receptors have revolutionized our current information about inducing and maximizing TRAIL mediated signaling in resistant prostate cancer phenotype. In this mini-review we outline outstanding developments in the field of prostate cancer that have played a role in understanding the underlying mechanisms that control TRAIL mediated apoptosis in prostate cancer cells, which may be helpful in the development of cancer therapies based on the apoptotic pathway.