Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth

Kaminski, Joseph; Hanlon, Alexandra L.; Joon, Daryl Lim; Meistrich, Marvin L.; Hachem, P.; Pollack, Alan

doi:10.1016/s0360-3016(03)00539-x

Cited by 58 publications

(29 citation statements)

References 13 publications

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“…Like cytotoxic agents, radiation cytotoxicity is known to be augmented by the suppression of AR signaling. Numerous lines of evidence have demonstrated that androgen deprivation augments the therapeutic effect of radiation (Granfors et al 1997, Zietman et al 1997, Kaminski et al 2003, Nishiyama 2012). In addition, clinical studies have also shown the favorable effects of castration in combination with radiation on locally advanced prostate cancer with intermediate and high risk (D'Amico et al 2004, Denham et al 2005.…”

Section: Pro-survival and Anti-apoptotic Roles Of Ar Signaling In Promentioning

confidence: 99%

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

Shiota

Yokomizo

Naito

2012

Endocrine-Related Cancer

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Oxidative stress caused by an increase in reactive oxygen species levels or a decrease in cellular antioxidant capacity can evoke the modulation of various cellular events including androgen receptor (AR) signaling via direct or indirect interactions. In this review, we summarize the mechanisms of AR activation by oxidative stress including: i) AR overexpression; ii) AR activation by AR co-regulators or intracellular signal transduction pathways; iii) generation of AR mutations or splice variants; and iv) de novo androgen synthesis. AR signaling augmented by oxidative stress appears to contribute to pro-survival and anti-apoptotic effects in prostate cancer cells in response to androgen deprivation therapy. In addition, AR signaling suppresses anti-survival and pro-apoptotic effects in prostate cancer cells in response to various cytotoxic and tumorsuppressive interventions including taxanes and radiation through the modulation of bIII-tubulin and ataxia telangiectasia-mutated kinase expression respectively. Taken together, AR signaling appears to render prostate cancer cells refractory to various therapeutic interventions including castration, taxanes, and radiation, indicating that AR signaling is a comprehensive resistant factor and crucial target for prostate cancer treatment.

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Section: Pro-survival and Anti-apoptotic Roles Of Ar Signaling In Promentioning

confidence: 99%

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

Shiota

Yokomizo

Naito

2012

Endocrine-Related Cancer

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“…42,43 Residual adrenal androgens 44 and de novo intratumoral androgen synthesis 45 effective when delivered after maximal tumor shrinkage in response to ADT, an effect that is almost completely lost if the tumor is allowed to re-grow in an androgen-independent manner following initial androgen ablation. [48][49][50] Many clinical trials are in line with these animal studies, reporting a biochemical response to neoadjuvant ADT independently predicts the survival benefit conferred by ADT with subsequent EBRT. [17][18][19][20][21][22][23] In addition, multivariate analysis in our trials 22,23 revealed high-risk prostate cancer patients who achieved a pre-EBRT PSA of <0.5 ng/ ml (versus >0.5 ng/ml) after neoadjuvant ADT displayed longer time to distant metastatic spread and had improved failure-free, prostate cancer-specific, and overall survival at a median follow-up of 7 years.…”

Section: Molecular Basis For Synergy Of Androgen Deprivation Therapy mentioning

confidence: 87%

Recent Developments in Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

Bader¹,

Černe²,

McGuire³

2014

Oncology &Amp; Hematology Review (US)

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133Prostate cancer is the most commonly diagnosed noncutaneous cancer and second leading cause of cancer mortality in American men. The lifetime risk for prostate cancer is estimated at one in six; 30,000 men die of the disease annually in the US.1 Prostate cancer is driven by the hormonally responsive transcription factor androgen receptor (AR) and the majority of prostate cancers are detected via serum level increase of the AR target gene prostate-specific antigen (PSA). Localized and low-risk prostate cancer is actively monitored or treated via radical prostatectomy (RP), brachytherapy, or external beam radiation therapy (EBRT). KeywordsLocally advanced prostate cancer (LAPC), androgen deprivation therapy (ADT), androgen receptor (AR), dose-escalation, external beam radiotherapy (EBRT), conformal radiotherapy (CRT), continuous and intermittent ADT (CAD, IAD), prostate specific antigen (PSA), castration resistant prostate cancer (CRPC), radiotherapy synergy, luteinizing hormone-releasing hormone (LHRH) analog, androgen receptor antagonist, anti-androgen, CYP17 inhibitor, molecular and metabolic markers, biomarkers

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“…17 In another in vivo study, RT and androgen-ablation sequencing were evaluated in the R33270G Dunning rat prostate tumor model. 18 It was found that the median posttreatment tumor doubling time was significantly longer in the group that received RT after neoadjuvant androgen ablation compared to all the other treatment groups, including the RT with concurrent or adjuvant androgen-deprived groups. The possible mechanism of ADT-EBRT interaction in that study was the diminished growth velocity of the surviving PC cells after neoadjuvant ADT.…”

Section: Rationales For Combined Treatment Adt-ebrtmentioning

confidence: 91%

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

Milecki¹

2010

CMAR

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Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

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Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth

Cited by 58 publications

References 13 publications

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

Recent Developments in Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

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