scholarly journals Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches

Oncogene ◽  
2013 ◽  
Vol 32 (49) ◽  
pp. 5501-5511 ◽  
Author(s):  
T Karantanos ◽  
P G Corn ◽  
T C Thompson
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Androgen Deprivation ◽  
Prostate Cancer Progression ◽  
Therapeutic Approaches ◽  
Novel Therapeutic

scholarly journals Androgen deprivation therapy promotes an obesity-like microenvironment in periprostatic fat

2019 ◽  
Vol 8 (5) ◽  
pp. 547-558 ◽  
Author(s):  
Stefano Mangiola ◽  
Ryan Stuchbery ◽  
Patrick McCoy ◽  
Ken Chow ◽  
Natalie Kurganovs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Side Effects ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Tissue Level ◽  
Androgen Deprivation ◽  
Clinical Settings ◽  
Prostate Cancer Development ◽  
Transcriptional Changes

Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between ADT, obesity, inflammation and prostate cancer progression is well established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castration therapies is missing. Here, we investigated the transcriptional changes in periprostatic fat tissue induced by profound ADT in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that the deprivation of androgen is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of therapies based on androgen deprivation may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.

scholarly journals Identification and Functional Characterization of a Novel Androgen Receptor Coregulator, EAP1

2021 ◽  
Vol 5 (11) ◽  
Author(s):  
Atsushi Yokoyama ◽  
Takumi Kouketsu ◽  
Yuri Otsubo ◽  
Erika Noro ◽  
Shun Sawatsubashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Functional Characterization ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Ubiquitin Ligase Activity ◽  
Transcriptional Coregulators ◽  
Endogenous Proteins

Abstract The androgen receptor (AR) plays an essential role in the development of prostate cancer, and androgen-deprivation therapy is used as a first-line treatment for prostate cancer. However, under androgen-deprivation therapy, castration-resistant prostate cancer inevitably arises, suggesting that the interacting transcriptional coregulators of AR are promising targets for developing novel therapeutics. In this study, we used novel proteomic techniques to evaluate the AR interactome, including biochemically labile binding proteins, which might go undetected by conventional purification methods. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, we identified enhanced at puberty 1 (EAP1) as a novel AR coregulator, whereas its interaction with AR could not be detected under standard biochemical conditions. EAP1 enhanced the transcriptional activity of AR via the E3 ubiquitin ligase activity, and its ubiquitination substrate proteins included AR and HDAC1. Furthermore, in prostate cancer specimens, EAP1 expression was significantly correlated with AR expression as well as a poor prognosis of prostate cancer. Together, these results suggest that EAP1 is a novel AR coregulator that promotes AR activity and potentially plays a role in prostate cancer progression.

Therapeutic Approaches Targeting Prostate Cancer Progression Using Novel Voltage-Gated Ion Channel Blockers

2003 ◽  
Vol 2 (3) ◽  
pp. 181-187 ◽  
Author(s):  
Robert A. Sikes ◽  
Alison M. Walls ◽  
W. Nathaniel Brennen ◽  
James D. Anderson ◽  
Indrani Choudhury-Mukherjee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ion Channel ◽  
Cancer Progression ◽  
Channel Blockers ◽  
Prostate Cancer Progression ◽  
Therapeutic Approaches ◽  
Voltage Gated ◽  
Ion Channel Blockers

scholarly journals KLF6 Loss of Function in Human Prostate Cancer Progression Is Implicated in Resistance to Androgen Deprivation

2012 ◽  
Vol 181 (3) ◽  
pp. 1007-1016 ◽  
Author(s):  
XiaoMei Liu ◽  
Alejandro Gomez-Pinillos ◽  
Charisse Loder ◽  
Enrique Carrillo-de Santa Pau ◽  
Ruifang Qiao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Androgen Deprivation ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression ◽  
Loss Of Function

scholarly journals Using Exercise and Nutrition to Alter Fat and Lean Mass in Men with Prostate Cancer Receiving Androgen Deprivation Therapy: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1664
Author(s):  
Rebekah L. Wilson ◽  
Dennis R. Taaffe ◽  
Robert U. Newton ◽  
Nicolas H. Hart ◽  
Philippa Lyons-Wall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Physical Function ◽  
Androgen Deprivation Therapy ◽  
Cancer Progression ◽  
Lean Mass ◽  
Resting Metabolic Rate ◽  
Androgen Deprivation ◽  
Increased Risk ◽  
Patient Reported

Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and physical function; however, effects on body composition have been variable. The aim of this review was to provide a descriptive overview and critical appraisal of exercise and nutrition-based interventions in prostate cancer patients on ADT and their effect on FM and LM. Our findings are that FM gain and LM loss are side effects of ADT that could be reduced, prevented, or even reversed with the implementation of a combined exercise and nutrition program. However, the most effective combination of specific exercise and nutrition prescriptions are yet to be determined, and thus should be a focus for future studies.

Sign in / Sign up

Export Citation Format

Share Document