Vitamin Bs, one carbon metabolism and prostate cancer.

Somatic genetic and epigenetic alterations have been suggested to be crucially involved in development and progression of cancers including prostate cancer (PCa). Epigenetic alterations such as chemical modification of chromatin associated proteins and DNA methylation can largely affect gene expression that may be important for early normal organ development, and also produces favorable conditions for cancer cell formation, growth, and survival. Aberrant DNA methylation (hyper- or hypo-methylation) may lead to chromosomal instability, and transcriptional gene silencing for tumor suppressors or overexpression for oncogenes. Vitamin Bs play important roles in one carbon metabolism that provides critical metabolites for DNA methylation, DNA repair and nucleic acid synthesis. Nutrition uptake and circulating levels of these vitamin Bs as well as genetic polymorphisms of related key enzymes in the one carbon metabolism pathway may govern bioavailability of the metabolites, and therefore to affect the phenotypic changes (e.g., cellular malignancy) via genetic and epigenetic alterations. This article will summarize recent new findings from laboratory, epidemiological or clinical trial studies regarding influence of vitamin B and one carbon metabolism on PCa development or progression.

Recent advances in understanding hormonal therapy resistant prostate cancer.

Androgen deprivation therapy has been the major treatment for advanced prostate cancer (PCa) and has shown to prolong life. However, remissions are temporary and patients almost inevitably progress to become castration-resistant prostate cancer (CRPC). CRPC is almost incurable even when treated with docetaxel that may have a slight life prolonging effect on CRPC patients. Interestingly, most of CRPC still express androgen receptor (AR) and depend on the AR for growth. Recently it has been suggested that AR may act as a tumor suppressor in normal prostatic epithelial cells, while in PCa cells AR becomes oncogenic, even under androgen deprivation states. The mechanisms for the latter are still under intensive investigations. A number of studies showed that, in fact, AR signaling is increased under an androgen-depleted environment. The mechanisms suggested in these studies including AR mutations, AR overexpression by gene amplification and other mechanisms that allow activation by low androgen levels or by other endogenous steroids, increased local de novo synthesis of androgens will be discussed. Moreover, developments and tests in clinical trials in CRPC of a number of novel agents interrupting AR signaling mediated PCa growth will also be discussed.