Efficacy of androgen deprivation therapy and the role of oxidative stress

Price, Donald D.

doi:10.1093/annonc/mdx001

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…Second, long-term ADT is associated with relatively advanced prostate cancer, which showed overexpression of VEGF [43]. In addition, oxidative stress occurs during the progression to castrationresistant prostate cancer, possibly masking the protective effect of ADT on neovascular AMD [44,45]. Third, administration of ADT can induce insulin resistance and metabolic syndrome, which are known risk factors of neovascular AMD [4,5].…”

Section: Discussionmentioning

confidence: 99%

Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer

Ha,

Kim,

Lee

et al. 2024

JCM

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Background/Objectives: to evaluate the association between androgen deprivation therapy (ADT) and newly developed neovascular age-related macular degeneration (AMD) in patients with prostate cancer. Methods: We identified 228,803 men from the nationwide claims database in the Republic of Korea diagnosed with prostate cancer between 1 August 2009 and 31 December 2018 and followed until April 2021. Cases were defined as those newly diagnosed with neovascular AMD during follow-up. Cases were matched with controls based on age, index date, and follow-up duration, at a case-to-control ratio of 1:4. Adjusted odds ratios (aORs) of incident neovascular AMD associated with ADT were estimated using conditional logistic regression. Results: The main analysis included 1700 cases and 6800 controls, with a median follow-up of 3.42 years. ADT was associated with a reduced risk of incident neovascular AMD in patients with prostate cancer (aOR = 0.840; 95% confidence interval [CI], 0.743–0.951; p = 0.0058) in the multivariable analysis. A cumulative ADT duration less than 1 year was associated with a reduced risk of neovascular AMD (aOR = 0.727; 95% CI, 0.610–0.866; p = 0.0004); however, no association was observed when the duration of ADT was between 1 and 2 years (aOR = 0.862; 95% CI, 0.693–1.074; p = 0.1854) or more than 2 years (aOR = 1.009; 95% CI, 0.830–1.226; p = 0.9304). Conclusions: In patients with prostate cancer, medical castration for less than a year is associated with a reduced risk of incident neovascular AMD. These results suggest that androgens are involved in the pathogenesis of neovascular AMD.

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Section: Discussionmentioning

confidence: 99%

Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer

Ha,

Kim,

Lee

et al. 2024

JCM

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“…However, increasing evidence suggests that ADT can induce oxidative stress by increasing ROS levels or decreasing cellular antioxidant system activity in surviving PC cells, which in turn cause genetic and epigenetic effects in PC. [29][30][31] Increased oxidative stress also causes redox signalling amplification and increases androgen receptor (AR) activation through several mechanisms, including AR overexpression, AR activation by co-regulators, mutation of AR and AR-related proteins, expression of AR splice variants, de novo androgen synthesis, etc. These alterations have pro-survival and anti-apoptotic effects on PC cells, resulting in the development of mCRPC.…”

Section: Discussionmentioning

confidence: 99%

“…The basic one, androgen deprivation therapy (ADT), is the first line of treatment against advanced PC and is also used as an adjuvant to local treatment in patients with high‐risk diseases. However, increasing evidence suggests that ADT can induce oxidative stress by increasing ROS levels or decreasing cellular antioxidant system activity in surviving PC cells, which in turn cause genetic and epigenetic effects in PC 29–31 . Increased oxidative stress also causes redox signalling amplification and increases androgen receptor (AR) activation through several mechanisms, including AR overexpression, AR activation by co‐regulators, mutation of AR and AR‐related proteins, expression of AR splice variants, de novo androgen synthesis, etc.…”

Section: Discussionmentioning

confidence: 99%

An in vitro redox adaptation model for metastatic prostate cancer: Establishing, characterizing and Cabazitaxel response evaluating

Eryılmaz

Egelí

Çeçener

2022

Clin Exp Pharma Physio

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Little is known about the redox-adapted cancer cells for understanding their pharmacologically targetable features and chemotherapeutic responses. Thus, we present the first in vitro redox adaptation model for metastatic prostate cancer (mPC), LNCaP-hydrogen peroxide resistant (LNCaP-HPR), with enhanced oxidative stress resistance accompanying poor Cabazitaxel response. After establishing, the cells were characterized by comparing the viability, death, oxidative stress, total glutathione (GSH) levels and the mRNA and protein levels of the redox-sensitive transcription factors responsible for the adaptation, Nrf-2, NF-κB and HIF-1α. Then, the apoptotic effect of Cabazitaxel was evaluated in LNCaP mPC, LNCaP-HPR and C4-2 metastatic castration-resistant (mCRPC) cells. In response to H 2 O 2 , viability, oxidative stress and the total GSH levels of LNCaP-HPR cells have confirmed the oxidative stress resistance. Nrf-2, NF-κB and HIF-1α were upregulated in LNCaP-HPR cells, not in LNCaP, confirming that resistant cells were much less affected by exogenous oxidative stress. Unlike LNCaP, LNCaP-HPR cells were less sensitive to Cabazitaxel, as closer to the response of C4-2 mCRPC cells, indicating that redox adaptation decreased Cabazitaxel response. This is the first evaluated association between redox adaptation and poor Cabazitaxel response, suggesting that in vitro Cabazitaxel efficiency is affected by PC cells' endogenous oxidative stress tolerance.

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“…Although clinical trials in castration-resistant CaP have led to availability of some drugs for therapeutic use, 49 there is always room to explore other avenues for therapy. An interesting angle to tackle oxidative stress may be through dietary antioxidant therapy.…”

Section: Discussionmentioning

confidence: 99%

Impact of Androgen Deprivation on Oxidative Stress and Antioxidant Status in Nigerian Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy

Bassey

Emodi

Akpan

et al. 2020

JCO Global Oncology

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PURPOSE Prostate cancer (CaP) incidence and mortality rate are increasing in Africa. Some have linked oxidative stress with the pathogenesis of cancer. This study assessed the levels of malondialdehyde (MDA), nitric oxide (NO), total plasma peroxide (TPP), and total antioxidant capacity (TAC) in Nigerian patients with CaP. PATIENTS AND METHODS One hundred twenty patients with CaP and 100 apparently healthy controls were consecutively recruited into this case-control study. The patients with CaP were divided into treatment-naïve and androgen deprivation therapy (ADT)–treated groups. Anthropometric indices were measured, and MDA, NO, TAC, and TPP were assayed by colorimetric methods. The t test and analysis of variance were used in analysis of data; statistical significance was set at P < .05, and 95% CIs were reported. RESULTS The patients with CaP had significantly higher waist-hip ratios and NO ( P = .0001), TPP ( P = .001), oxidative stress index (OSI; P = .003), and MDA values ( P = .002) than controls. The treatment-naive patients with CaP had significantly higher waist-hip ratios ( P = .011) and TPP ( P = .013), MDA ( P = .011), and NO values ( P = .0001) and lower TAC values ( P = .013) compared with the controls. The ADT-treated patients had higher waist-hip ratios ( P = .0001) and TPP ( P = .005), OSI ( P = .005), MDA ( P = .011), and NO values ( P = .0001) than the controls. However, the treatment-naive patients had significantly higher NO values ( P = .05) only compared with the ADT-treated patients. There was a significantly positive correlation between MDA and duration of treatment ( r = 0.280, P = .018) in ADT-treated patients with CaP. CONCLUSION This study demonstrated that patients with CaP have higher levels of TPP, MDA, and NO and lower levels of TAC compared with men without CaP. In addition, even in patients with CaP undergoing treatment, TPP and MDA levels remained high.

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Efficacy of androgen deprivation therapy and the role of oxidative stress

Cited by 5 publications

References 16 publications

Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer

Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer

An in vitro redox adaptation model for metastatic prostate cancer: Establishing, characterizing and Cabazitaxel response evaluating

Impact of Androgen Deprivation on Oxidative Stress and Antioxidant Status in Nigerian Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy

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