High-risk prostate cancer: A disease of genomic instability

Tapia-Laliena, María Ángeles; Korzeniewski, Nina; Hohenfellner, Markus; Duensing, Stefan

doi:10.1016/j.urolonc.2014.02.005

Cited by 32 publications

(23 citation statements)

References 56 publications

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“…In high Gleason samples, we generally observed less significant metabolic and transcriptomic alterations due to ERG status. High Gleason score has been linked to genomic instability and multiple genetic alterations [40, 41]. As the high Gleason samples are heterogeneous, the transcriptomic- and metabolic differences between ERG high and ERG low may possibly be masked by the effect of other genetic alterations present among these samples.…”

Section: Resultsmentioning

confidence: 99%

Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer

et al. 2016

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TMPRSS2-ERG has been proposed to be a prognostic marker for prostate cancer. The aim of this study was to identify changes in metabolism, genes and biochemical recurrence related to TMPRSS2-ERG by using an integrated approach, combining metabolomics, transcriptomics, histopathology and clinical data in a cohort of 129 human prostate samples (41 patients). Metabolic analyses revealed lower concentrations of citrate and spermine comparing ERGhigh to ERGlow samples, suggesting an increased cancer aggressiveness of ERGhigh compared to ERGlow. These results could be validated in a separate cohort, consisting of 40 samples (40 patients), and magnetic resonance spectroscopy imaging (MRSI) indicated an in vivo translational potential. Alterations of gene expression levels associated with key enzymes in the metabolism of citrate and polyamines were in consistence with the metabolic results. Furthermore, the metabolic alterations between ERGhigh and ERGlow were more pronounced in low Gleason samples than in high Gleason samples, suggesting it as a potential tool for risk stratification. However, no significant difference in biochemical recurrence was detected, although a trend towards significance was detected for low Gleason samples. Using an integrated approach, this study suggests TMPRSS2-ERG as a potential risk stratification tool for inclusion of active surveillance patients.

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Section: Resultsmentioning

confidence: 99%

Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer

et al. 2016

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“…DNA damage response (DDR) refers to coordinated cellular mechanisms that prevent DNA damage accumulation and maintain genomic integrity (Karanika et al, 2014) and plays a central role in PCa initiation, development and progression (Tapia-Laliena et al, 2014). AR signaling in PCa cells has been associated with numerous aspects of DDR pathways including regulation of ATM-Chk2 signaling for initiation of DDR (Ide et al, 2012), poly(ADP-ribose) polymerase function (Schiewer et al, 2012) and non-homologous end joining recombination (Polkinghorn et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling

Karanika

Karantanos

et al. 2017

Cell Reports

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“…Human prostate cancer develops as normal prostate epithelium acquires a series of mutations and epigenetic changes that lead to invasive adenocarcinoma of the prostate (23). Further mutations lead to development of metastatic prostate cancer that spreads to other organs.…”

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confidence: 99%

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

Puckett

Antinozzi

et al. 2015

J Virol

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A major challenge to oncolytic virus therapy is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type. Variability in response may arise due to differences in the initial genetic lesions leading to cancer development. Alternatively, susceptibility to viral oncolysis may change during cancer progression. These hypotheses were tested using cells from a transgenic mouse model of prostate cancer infected with vesicular stomatitis virus (VSV). Primary cultures from murine cancers derived from prostate-specific Pten deletion contained a mixture of cells that were susceptible and resistant to VSV. Castration-resistant cancers contained a higher percentage of susceptible cells than cancers from non- T here has been a great deal of progress in the development of new replication-competent viruses that kill cancer cells (oncolytic viruses), in understanding their mechanisms of oncolysis, and in their advancement to clinical trials (1-3). The key biological underpinning of oncolytic virus therapy is that activation of proliferative signaling pathways in cancer cells often leads to downregulation of antiviral pathways, making cancer cells more susceptible to virus infection than normal cells (4-7). Vesicular stomatitis virus (VSV) is a well-established example of a highly cytolytic virus with a tropism for cancers that have downregulated their antiviral responses (5). Our laboratory and others have made a variety of genetic modifications to enhance the selectivity of VSV for cancers versus normal tissues (7-14). For example, viruses with mutations in the viral M protein, which is responsible for suppressing host antiviral responses, are defective in their ability to invade normal tissues (15, 16) but effectively infect cancers that are defective in their antiviral responses (3). Genetically engineered VSV is currently in a phase I clinical trial for localized treatment of hepatocellular carcinoma (2). However, one of the major challenges to oncolytic virus therapy is that individual cancer cell lines vary dramatically in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type (7,13,(17)(18)(19)(20)(21)(22). The experiments presented here address the origin of these differences in susceptibility to oncolytic VSV among prostate cancers.Human prostate cancer develops as normal prostate epithelium acquires a series of mutations and epigenetic changes that lead to invasive adenocarcinoma of the prostate (23). Further mutations lead to development of metastatic prostate cancer that spreads to other organs. For patients with localized prostate cancer, radiation therapy and/or radical prostatectomy typically achieve Ͼ90% disease-free survival within 5 years (24, 25). How-

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High-risk prostate cancer: A disease of genomic instability

Cited by 32 publications

References 56 publications

Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer

Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer

Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

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