Molecular Pathways in Prostate Cancer

OBJECTIVES: Prostate cancer is a prevalent disease with a high impact on patients’ morbidity and mortality. Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with disease progression remain partially elusive. The purpose of this study is to review the recent evidence relating to the initiation and progression of prostate cancer in relation to the familial correlation of the disease, the genetic aberrations resulting in prostate cancer and the new molecular biology data regarding prostate cancer. MATERIALS AND METHODS: A Medline database search identified all the existing publications on the molecular events associated with the pathogenesis and evolution of prostate cancer. Particular emphasis was given on the specific genetic phenomena associated with prostate cancer. RESULTS: Like other cancers, prostate cancer is caused by an accumulation of genetic alterations in a cell that drives it to malignant growth. Specific genes and gene alterations have been suggested to play a role in its development and progression. Aneuploidy, loss of heterozygosity, gene mutations, hypermethylation and inactivation of specific tumour suppressor genes such as GSTpi, APC, MDR1, GPX3 and others have been detected in prostate cancers, but generally only at a low or moderate frequency. The androgen receptor (AR) signalling pathway may play a crucial role in the early development of prostate cancer, as well as in the development of androgen-independent disease that fails to respond to hormone deprivation therapies. Other alterations linked to the transition to hormone-independence include amplification of MYC and increased expression of ERBB2 and BCL2. Inflammatory changes may also contribute to the development of prostate cancer. CONCLUSION: The identification of specific molecular markers for prostate cancer may lead to its earliest detection and better prediction of its behavior. The better understanding of the molecular events affecting prostate cancer progression may result in the introduction of new drugs to target these events thus providing a potential cure and a tool for prevention of this very common disease.