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
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
3946-3952Informations 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.
Références
Gene. 2020 May 20;739:144498
pubmed: 32097694
Int J Cancer. 2019 Jan 15;144(2):221-231
pubmed: 30246379
Cancer Res. 2016 Feb 15;76(4):831-43
pubmed: 26747897
Proc Natl Acad Sci U S A. 2016 May 31;113(22):6259-64
pubmed: 27185910
Urol Oncol. 2020 Nov;38(11):801-815
pubmed: 32591248
Urologe A. 2020 Jun;59(6):673-679
pubmed: 32274540
J Cell Biochem. 2019 Aug;120(8):12247-12258
pubmed: 30864186
J Breast Cancer. 2014 Mar;17(1):40-6
pubmed: 24744796
J Clin Invest. 2018 Jul 2;128(7):2979-2995
pubmed: 29863497
Cancers (Basel). 2011 Mar 1;3(1):1383-404
pubmed: 21544224
N Engl J Med. 2020 May 28;382(22):2091-2102
pubmed: 32343890
Eur Urol. 2018 Feb;73(2):178-211
pubmed: 28655541
J Clin Pathol. 1995 Sep;48(9):876-8
pubmed: 7490328
Nat Rev Mol Cell Biol. 2012 Apr 04;13(5):297-311
pubmed: 22473470
Cell. 2007 May 18;129(4):823-37
pubmed: 17512414