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Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation

1
Department of Primary Health Care, University of Pécs, Rákóczi u 2, H-7623 Pécs, Hungary
2
Faculty of Health Sciences, Doctoral School of Health Sciences, University of Pécs, Vörösmarty u 4, H-7621 Pécs, Hungary
3
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland
4
Institute of Sport Sciences and Physical Education, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary
5
Faculty of Sciences, Doctoral School of Biology and Sportbiology, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary
6
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia
*
Author to whom correspondence should be addressed.
Genes 2019, 10(8), 599; https://doi.org/10.3390/genes10080599
Received: 17 June 2019 / Revised: 2 August 2019 / Accepted: 5 August 2019 / Published: 8 August 2019
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PDF [264 KB, uploaded 8 August 2019]

Abstract

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes. View Full-Text
Keywords: castration resistant prostate cancer; docetaxel; pharmacogenomic biomarker; personalised treatment castration resistant prostate cancer; docetaxel; pharmacogenomic biomarker; personalised treatment
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Varnai, R.; Koskinen, L.M.; Mäntylä, L.E.; Szabo, I.; FitzGerald, L.M.; Sipeky, C. Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation. Genes 2019, 10, 599.

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