Punit Saraon1, Keith Jarvi, Eleftherios P Diamandis. 1. Samuel Lunenfeld Research Institute and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
Abstract
BACKGROUND: Prostate cancer is the most commonly diagnosed cancer among men in North America and is a leading cause of death. Standard treatments include androgen deprivation therapy, which leads to improved clinical outcomes. However, over time, most tumors become androgen independent and no longer respond to hormonal therapies. Several mechanisms have been implicated in the progression of prostate cancer to androgen independence. CONTENT: Most tumors that have become androgen independent still rely on androgen receptor (AR) signaling. Mechanisms that enhance AR signaling in androgen-depleted conditions include: AR gene amplification, AR mutations, changes in the balance of AR cofactors, increases in steroidogenic precursors, and activation via "outlaw" pathways. Along with AR signaling, various other AR-independent "bypass" pathways have been shown to operate aberrantly during androgen independence. Changes in the epigenetic signatures and microRNA concentrations have also been implicated in the development of androgen-independent prostate cancer. SUMMARY: Understanding of the molecular mechanisms that lead to the development of androgen-independent prostate cancer will allow for improved therapeutic strategies that target key pathways and molecules that are essential for these cells to survive.
BACKGROUND:Prostate cancer is the most commonly diagnosed cancer among men in North America and is a leading cause of death. Standard treatments include androgen deprivation therapy, which leads to improved clinical outcomes. However, over time, most tumors become androgen independent and no longer respond to hormonal therapies. Several mechanisms have been implicated in the progression of prostate cancer to androgen independence. CONTENT: Most tumors that have become androgen independent still rely on androgen receptor (AR) signaling. Mechanisms that enhance AR signaling in androgen-depleted conditions include: AR gene amplification, AR mutations, changes in the balance of AR cofactors, increases in steroidogenic precursors, and activation via "outlaw" pathways. Along with AR signaling, various other AR-independent "bypass" pathways have been shown to operate aberrantly during androgen independence. Changes in the epigenetic signatures and microRNA concentrations have also been implicated in the development of androgen-independent prostate cancer. SUMMARY: Understanding of the molecular mechanisms that lead to the development of androgen-independent prostate cancer will allow for improved therapeutic strategies that target key pathways and molecules that are essential for these cells to survive.
Authors: Scott Gross; Pranava Mallu; Hinal Joshi; Bryant Schultz; Christina Go; Jonathan Soboloff Journal: Adv Cancer Res Date: 2020-07-09 Impact factor: 6.242
Authors: Steven L Wood; Margaret A Knowles; Douglas Thompson; Peter J Selby; Rosamonde E Banks Journal: Nat Rev Urol Date: 2013-02-26 Impact factor: 14.432
Authors: Punit Saraon; Natasha Musrap; Daniela Cretu; George S Karagiannis; Ihor Batruch; Chris Smith; Andrei P Drabovich; Dominique Trudel; Theodorus van der Kwast; Colm Morrissey; Keith A Jarvi; Eleftherios P Diamandis Journal: J Biol Chem Date: 2012-08-20 Impact factor: 5.157
Authors: Punit Saraon; Daniela Cretu; Natasha Musrap; George S Karagiannis; Ihor Batruch; Andrei P Drabovich; Theodorus van der Kwast; Atsushi Mizokami; Colm Morrissey; Keith Jarvi; Eleftherios P Diamandis Journal: Mol Cell Proteomics Date: 2013-02-26 Impact factor: 5.911