Influence of Number of CAG Repeats on Local Control in the RTOG 86-10 Protocol

Abdel‐Wahab, May; Berkey, Brian; Krishan, Awtar; O'Brien, Tom; Hammond, Elizabeth H.; Roach, Mack; Lawton, C.A.; Pilepich, Milijenko; Markoe, Arnold M.; Pollack, Alan

doi:10.1097/01.coc.0000195085.34162.88

Cited by 17 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we had the opportunity to evaluate VEGF levels in the well-characterized RTOG 8610 patient population. There have been a number of other biomarker studies done in this patient population already, and this study complements what is known for this patient population [45-51]. However, with the limitations presented, we acknowledge that this secondary analysis of RTOG 8610 will not serve to make the definitive statement regarding whether VEGF is a useful biomarker or not, but reporting on this well-characterized patient population with long-term follow-up and numerous other biomarker publications arising from this population is in our opinion a significant contribution to the current heterogeneous VEGF literature [18-28,31-34].…”

Section: Discussionsupporting

confidence: 54%

Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

et al. 2013

Self Cite

View full text Add to dashboard Cite

BackgroundAngiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer.MethodsThe analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0–3). Cox or Fine and Gray’s proportional hazards models were used.ResultsSufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm.ConclusionsThis study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of human prostate cancer biomarkers.

show abstract

Section: Discussionsupporting

confidence: 54%

Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although several studies have attempted to determine the role of AR -CAG repeat length on the outcomes of ADT, the results remain uncertain. Some studies showed that shorter CAG repeat length was correlated with better responses to hormonal therapy [30], [31], an observation consistent with the present study. On the other hand, other studies found that patients with better clinical responses to ADT had a longer CAG repeat length [32], [33], or in some cases, no correlation was found [34]–[37].…”

Section: Discussionsupporting

confidence: 92%

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Huang

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P≤0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.

show abstract

“…Pretreatment serum levels of testosterone or adrenal androgens were considered, but were modestly predictive of response to ADT [112][113][114][115]. At the molecular level, ADT response was associated with AR (variant) expression levels [116], length of AR CAG repeats that affect activity of AR [117,118], expression of steroidogenic enzymes targeted by ADT such as CYP17A1 [119], and germline polymorphisms in androgen transporters [120]. Expression status of two AR target genes, PSA and PSMA, in CaP circulating tumor cells, were used as a measure of AR activity and correlated with CaP response to ADT [121].…”

Section: Future Directionsmentioning

confidence: 99%

Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer

Chauhan

Heemers

2021

Cancers

View full text Add to dashboard Cite

Inhibiting the activity of the ligand-activated transcription factor androgen receptor (AR) is the default first-line treatment for metastatic prostate cancer (CaP). Androgen deprivation therapy (ADT) induces remissions, however, their duration varies widely among patients. The reason for this heterogeneity is not known. A better understanding of its molecular basis may improve treatment plans and patient survival. AR’s transcriptional activity is regulated in a context-dependent manner and relies on an interplay between its associated transcriptional regulators, DNA recognition motifs, and ligands. Alterations in one or more of these factors induce shifts in the AR cistrome and transcriptional output. Significant variability in AR activity is seen in both castration-sensitive (CS) and castration-resistant CaP (CRPC). Several AR transcriptional regulators undergo somatic alterations that impact their function in clinical CaPs. Some alterations occur in a significant fraction of cases, resulting in CaP subtypes, while others affect only a few percent of CaPs. Evidence is emerging that these alterations may impact the response to CaP treatments such as ADT, radiation therapy, and chemotherapy. Here, we review the contribution of recurring somatic alterations on AR cistrome and transcriptional output and the efficacy of CaP treatments and explore strategies to use these insights to improve treatment plans and outcomes for CaP patients.

show abstract

Influence of Number of CAG Repeats on Local Control in the RTOG 86-10 Protocol

Abstract: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

Cited by 17 publications

References 38 publications

Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer

Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer

Contact Info

Product

Resources

About