KDM5D predicts response to docetaxel chemotherapy in metastatic castration resistant prostate cancer patients.

KDM5D biomarker docetaxel chemotherapy in situ hybridization (ISH) metastatic castration resistant prostate cancer (mCRPC) therapy response

Journal

Translational andrology and urology
ISSN: 2223-4691
Titre abrégé: Transl Androl Urol
Pays: China
ID NLM: 101581119

Informations de publication

Date de publication:
Oct 2021
Historique:
received: 20 07 2020
accepted: 21 01 2021
entrez: 22 11 2021
pubmed: 23 11 2021
medline: 23 11 2021
Statut: ppublish

Résumé

The administration of docetaxel chemotherapy is one therapeutic option to delay disease progression and increase overall survival in metastatic castration resistant prostate cancer (mCRPC). However, about 15% of patients are primary resistant to chemotherapy and hence would benefit from an alternative mCRPC treatment. Despite intensive research, there are no robust clinical validated biomarkers to predict mCRPC therapy response. Thus, the aim of the study was to determine KDM5D expression in archival radical prostatectomy specimens of patients medicated with docetaxel at time of mCRPC development in order to correlate KMD5D expression with treatment response. We used in situ hybridization (ISH) (RNA scope 2.5 HD) to determine KDM5D expression in tissue samples of 28 prostate cancer patients. KDM5D status was correlated to chemotherapy response (PSA and radiographic response). Data revealed that KDM5D is significantly overexpressed in tumor cells (P<0.0001) but also in benign cells (P<0.02) of those patients who responded to chemotherapy compared to non-responders. To summarize, KDM5D is a promising novel biomarker predicting response to docetaxel chemotherapy already at the time of localized disease and thus potentially avoiding metastatic biopsies in the mCRPC stage of disease.

Sections du résumé

BACKGROUND BACKGROUND
The administration of docetaxel chemotherapy is one therapeutic option to delay disease progression and increase overall survival in metastatic castration resistant prostate cancer (mCRPC). However, about 15% of patients are primary resistant to chemotherapy and hence would benefit from an alternative mCRPC treatment. Despite intensive research, there are no robust clinical validated biomarkers to predict mCRPC therapy response. Thus, the aim of the study was to determine KDM5D expression in archival radical prostatectomy specimens of patients medicated with docetaxel at time of mCRPC development in order to correlate KMD5D expression with treatment response.
METHODS METHODS
We used in situ hybridization (ISH) (RNA scope 2.5 HD) to determine KDM5D expression in tissue samples of 28 prostate cancer patients. KDM5D status was correlated to chemotherapy response (PSA and radiographic response).
RESULTS RESULTS
Data revealed that KDM5D is significantly overexpressed in tumor cells (P<0.0001) but also in benign cells (P<0.02) of those patients who responded to chemotherapy compared to non-responders.
CONCLUSIONS CONCLUSIONS
To summarize, KDM5D is a promising novel biomarker predicting response to docetaxel chemotherapy already at the time of localized disease and thus potentially avoiding metastatic biopsies in the mCRPC stage of disease.

Identifiants

pubmed: 34804837
doi: 10.21037/tau-20-1084
pii: tau-10-10-3946
pmc: PMC8575572
doi:

Types de publication

Journal Article

Langues

eng

Pagination

3946-3952

Informations de copyright

2021 Translational Andrology and Urology. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1084). The series “Management of Advanced Genitourinary Malignancies” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

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Auteurs

Georg Schäfer (G)

Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria.

Nikola Bednarova (N)

Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

Axel Heidenreich (A)

Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urological Surgery, University Hospital Cologne, Cologne, Germany.

Helmut Klocker (H)

Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

Isabel Heidegger (I)

Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

Classifications MeSH