Cancer of the prostate forms the 2nd most common class of cancer in males in the Western world and accounts for 40,000 deaths per year in the US alone. Prostate cancer cells are characterized by slow growth kinetics and conventional cytotoxic agents which target rapidly dividing cells are generally poorly active in prostate cancer. On the other hand the apoptotic machinery is in place even in metastatic cancer and in fact a high apoptotic index is a feature of tumor biopsies and this becomes more pronounced with increasing grade of tumor. Strategies for activating apoptosis pathways may therefore be particularly well suited to this disease. The potential value of using apoptotic drugs in the treatment of cancer has driven the pharmaceutical industry to treat the development of this therapeutic class as a high priority with over 100 products being listed in development in 2001. New targets are continuously being sought, with K+ representing one such target since increased efflux is an early event in apoptosis. Researchers at Case Western Reserve University have been investigating KChAP/PIAS3beta which is a K+ channel modulatory protein that boosts expression of a subset of K+ channels and increases currents without affecting gating. In addition this protein interacts with a variety of transcription factors including the pro-apoptotic protein, p53. Considering it's involvement at multiple steps of the apoptosis machinery, it is perhaps unsurprising that transfecting LNCaP cells, a prostate cancer cell line that expresses both K+ currents and wild-type p53, with KChAP has recently been shown to induce apoptosis. The apoptotic effects of KChAP were direct and also involved the facilitation of other apoptotic pathways. Apoptotic activity was mirrored by both increased K+ efflux and p53 activation however the latter was not obligatory since KChAP also induced apoptosis in DU145 cells, a prostate cancer cell line with mutant p53. KChAP prevented growth of DU145 and LNCaP tumor xenografts in nude mice indicating that targeting KChAP might represent a novel method of cancer treatment

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