Cancer stem cells in prostate adenocarcinoma: a target for new anticancer strategies.

Prostate cancer (PC) is major common malignancy in males in most industrialized Western countries, where it is the most commonly diagnosed cancer affecting men after middle age (>50 years). Over 90% of PC patients with incurable disease respond to primary treatment, which consists of intervention to lower serum testosterone. However, the duration of response is short (12-33 months) and in almost all patients, is followed by the emergence of a phenotype resistant to androgen deprivation in therapy (known as hormone or androgen-resistant PC). Considerable research efforts have been directed towards the identification of markers associated with the initiation and progression of PC, yet there is little consensus about the target cell within prostate epithelium that is susceptible to malignant transformation. Stem cells may represent a major target for mutations leading to cancer as their longevity assures continued presence during the long latency between carcinogenic agents exposure and cancer development. Therefore in order to allow the development of more effective treatment strategies for PC, a better understanding of the molecular changes that underlie cancer stem cells is required.

A case of human polyomavirus Bk infection in a patient affected by late stage prostate cancer: could viral infection be correlated with cancer progression?

The basic molecular mechanisms regulating prostate cancer (PCA) development and progression are very poorly understood. Different tumor suppressor genes are implicated in PCA. In particular, since the mutation rate of the p53 gene is also low, researchers have speculated that an infectious agent might play an important role in PCA. Polyomaviruses are candidates for this agent. We selected a patient with a diagnosis of PCA and underwent radical prostatectomy, to investigate the presence of polyomavirus BK (BKV) sequences (urine and neoplastic tissues) and the mutation pattern of p53 gene. The results obtained showed the presence of BKV DNA and of p53 gene mutations in exons 6, 8 and 9. We speculate that BKV might contribute to cellular transformation process, triggered possibly by p53 gene mutations.

New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma.

In this review, we will present some of the information that is known about neuroendocrine (NE) cells and differentiation in the prostate. We will then speculate on the potential role that NE differentiation in prostate carcinoma may play and how this differentiation may be clinically analysed and treated. The androgen-independent growth of prostate cancer can be caused by different mechanisms; one of these is receptor-specific paracrine or autocrine growth modulation of human prostatic cancer cells by neuropeptides secreted by NE cells. Our results affirm that different methods of androgen deprivation can influence the serum chromogranin A (CgA) levels to different extents in prostate cancer. In particular, bicalutamide produces a significantly lower increase in serum CgA compared with castration therapy. In the light of other evidence that supports a significant relationship between serum CgA levels, tissue CgA expression and NE activity, we hypothesise that bicalutamide may reduce the risk of NE cell hyperactivation in prostate cancer. It is important to determine whether increases in CgA levels and NE cell activation are associated with progression towards hormone-independent prostate cancer. We recently proposed as therapy of NE activation in hormone-independent prostate cancer, a combination of oestrogens and somatostatin analogues. The combination of ethinyl estradiol and lanreotide had a favourable toxicity profile, offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies and, in particular, offered a median overall survival that was superior to the 10-month median survival in patients with hormone refractory disease. This combination therapy also sustains the novel concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment in combination, which can confer protection from apoptosis.