New Biomarkers for Selecting the Best Therapy Regimens in Metastatic Castration-Resistant Prostate Cancer

Heidegger, Isabel; Heidenreich, Axel; Pfister, David

doi:10.1007/s11523-016-0461-6

Cited by 10 publications

(6 citation statements)

References 72 publications

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“…Prostate cancer (PCa) is the most frequent male cancer in Western societies followed by lung and colon cancer [1]. Disease stages range from slow-growing local tumors to aggressive stages with high metastatic potential [2]. Because of the strong relevance of androgens, androgen deprivation therapy (ADT) is a mainstay in the treatment of metastatic prostate cancer (mPCa).…”

Section: Introductionmentioning

confidence: 99%

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer

Ladurner

Wieser²,

Eigentler

et al. 2021

Biomedicines

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Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

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Section: Introductionmentioning

confidence: 99%

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer

Ladurner

Wieser²,

Eigentler

et al. 2021

Biomedicines

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show abstract

“…However, after a time of about 2-3 years, patients experience resistance to androgen deprivation therapy (metastatic castration-resistant prostate cancer, mCRPC). In the past five years, several new therapeutic options targeting the androgen receptor (AR)-signaling axis have been developed for this patient population, including the AR-inhibiting agent enzalutamide [5,6]. Response to these drugs, however, is only temporary, as the majority of treated patients develop drug resistance.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Cand1 in Prostate Cancer

Eigentler

Tymoszuk

Zwick

et al. 2020

Cancers

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Evidence has accumulated asserting the importance of cullin-RING (really interesting new gene) ubiquitin ligases (CRLs) and their regulator Cullin-associated neural-precursor-cell-expressed developmentally down-regulated 8 (NEDD8) dissociated protein 1 (Cand1) in various cancer entities. However, the role of Cand1 in prostate cancer (PCa) has not been intensively investigated so far. Thus, in the present study, we aimed to assess the relevance of Cand1 in the clinical and preclinical setting. Immunohistochemical analyses of radical prostatectomy specimens of PCa patients showed that Cand1 protein levels are elevated in PCa compared to benign areas. In addition, high Cand1 levels were associated with higher Gleason Scores, as well as higher tumor recurrence and decreased overall survival. In line with clinical findings, in vitro experiments in different PCa cell lines revealed that knockdown of Cand1 reduced cell viability and proliferation and increased apoptosis, therefore underlining its role in tumor progression. We also found that the cyclin-dependent kinase inhibitor p21 is significantly upregulated upon downregulation of Cand1. Using bioinformatic tools, we detected genes encoding for proteins linked to mRNA turnover, protein polyubiquitination, and proteasomal degradation to be significantly upregulated in Cand1high tumors. Next generation sequencing of PCa cell lines resistant to the anti-androgen enzalutamide revealed that Cand1 is mutated in enzalutamide-resistant cells, however, with little functional and clinically relevant impact in the process of resistance development. To summarize the present study, we found that high Cand1 levels correlate with PCa aggressiveness.

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“…Prostate cancer is the most common cancer in men and a leading cause of cancer death among men in developed countries ( 1 ). In recent years, several new targeted therapeutic agents become standard treatment options in metastatic castration-resistant prostate cancer (mCRPC) including androgen receptor targeting agents (abiraterone, enzalutamide) or taxane based chemotherapeutic agents (docetaxel, cabazitaxel) after showing prolongation of overall survival (OS) in corresponding phase III clinical studies compared with standard of care ( 2 ).…”

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confidence: 99%

“…Concerning response rates and side effects of radium-223 the ECOG performance status, skeletal tumor burden, alkaline phosphatase (ALP) as well as the Bone Scan Index have been reported to be promising biomarkers for both OS and hematological toxicities in patients with radium-223 therapy ( 2 , 10 )…”

mentioning

confidence: 99%

Radium-223 for metastatic castration-resistant prostate cancer: results and remaining open issues after the ALSYMPCA trial

Heidegger

Pichler

Heidenreich

et al. 2018

Transl. Androl. Urol.

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New Biomarkers for Selecting the Best Therapy Regimens in Metastatic Castration-Resistant Prostate Cancer

Cited by 10 publications

References 72 publications

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer

The Impact of Cand1 in Prostate Cancer

Radium-223 for metastatic castration-resistant prostate cancer: results and remaining open issues after the ALSYMPCA trial

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