To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

Cancers

Kai-Xin Zhang¹  Jessica Firus¹  Brenda Prieur¹  William Jia² 

[1] The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6, Canada; E-Mails:;Department of Surgery and Brain Research Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; E-Mail:

关键词: prostate cancer;    cell death mechanisms;    apoptosis;    progression;    castration resistance;   

DOI  :  10.3390/cancers3021498

来源: mdpi

【 摘 要 】

Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.