Molecular Pathways in Prostate Cancer

Abstract

ObjectivesProstate 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 MethodsA 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.ResultsLike 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.ConclusionThe 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.

Molecular Imaging of Prostate Cancer

“…Prostate cancer ranges from slowly growing, indolent intraprostatic tumors to rapidly progressive metastasizing and therapy-resistant clones (2). A considerable proportion of prostate cancers will not affect the life expectancy of patients, as suggested by investigators in a recent meta-analysis of the results of 19 autopsy studies; these investigators found that among men aged 70-79 years, tumor had been discovered in 36% of white men and 51% of African American men (3).…”

NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer

“…[7][8][9][10][11] AR can promote ligand-independent prostate cancer progression by directly regulating the transcription of c-Myc, 30 which confers androgen independence. 29 As a target gene of c-Myc, 17 NDRG2 has been widely accepted as a tumor suppressor in many types of cancers, 15,21,[25][26][27] and our previous study reported a negative correlation between the expression of NDRG2 and that of c-Myc in prostate cancer.…”

“…6 Several mechanisms underlying castration resistance have been documented, including (a) AR mutations or amplification, (b) alterations in the balance between AR and its transcriptional co-regulators and (c) growth factors/kinases signal pathways that activate AR activity at postcastration androgen levels. [7][8][9][10][11] It is noteworthy that CRPC cells retain AR and AR-regulated gene expression in the absence of or with low levels of circulating androgens. 12 In addition, tumors that are refractory to conventional androgen deprivation therapy are susceptible to more potent androgen pathway inhibitors.…”

Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

“…The progression of prostate cancer normally goes from castration-sensitive to castration-resistant, inevitably developing highly metastatic properties (3,4). Androgen deprivation therapy (ADT) is the main therapeutic approach for patients with metastatic prostate cancer (5). Prostate cancer patients respond initially to ADT, but in later stages the tumor becomes hormone refractory and more aggressive, eventually leading to poor prognosis (5).…”

“…Androgen deprivation therapy (ADT) is the main therapeutic approach for patients with metastatic prostate cancer (5). Prostate cancer patients respond initially to ADT, but in later stages the tumor becomes hormone refractory and more aggressive, eventually leading to poor prognosis (5).…”