Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer

From discovery to implementation

Reka Varnai, Leena M. Koskinen, Laura E. Mäntylä, Istvan Szabo, Liesel M. Fitzgerald, C. Sipeky

Research output: Contribution to journalReview article

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.

Original languageEnglish
Article number599
JournalGenes
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 1 2019

Fingerprint

docetaxel
Pharmacogenetics
Prostatic Neoplasms
Biomarkers
Therapeutics
Precision Medicine
Castration
Tumor Biomarkers

Keywords

  • Castration resistant prostate cancer
  • Docetaxel
  • Personalised treatment
  • Pharmacogenomic biomarker

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer : From discovery to implementation. / Varnai, Reka; Koskinen, Leena M.; Mäntylä, Laura E.; Szabo, Istvan; Fitzgerald, Liesel M.; Sipeky, C.

In: Genes, Vol. 10, No. 8, 599, 01.08.2019.

Research output: Contribution to journalReview article

Varnai, Reka ; Koskinen, Leena M. ; Mäntylä, Laura E. ; Szabo, Istvan ; Fitzgerald, Liesel M. ; Sipeky, C. / Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer : From discovery to implementation. In: Genes. 2019 ; Vol. 10, No. 8.
@article{968e500b5e6749b2bce30e04306dd0a9,
title = "Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer: From discovery to implementation",
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.",
keywords = "Castration resistant prostate cancer, Docetaxel, Personalised treatment, Pharmacogenomic biomarker",
author = "Reka Varnai and Koskinen, {Leena M.} and M{\"a}ntyl{\"a}, {Laura E.} and Istvan Szabo and Fitzgerald, {Liesel M.} and C. Sipeky",
year = "2019",
month = "8",
day = "1",
doi = "10.3390/genes10080599",
language = "English",
volume = "10",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

TY - JOUR

T1 - Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer

T2 - From discovery to implementation

AU - Varnai, Reka

AU - Koskinen, Leena M.

AU - Mäntylä, Laura E.

AU - Szabo, Istvan

AU - Fitzgerald, Liesel M.

AU - Sipeky, C.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - Castration resistant prostate cancer

KW - Docetaxel

KW - Personalised treatment

KW - Pharmacogenomic biomarker

UR - http://www.scopus.com/inward/record.url?scp=85071158637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071158637&partnerID=8YFLogxK

U2 - 10.3390/genes10080599

DO - 10.3390/genes10080599

M3 - Review article

VL - 10

JO - Genes

JF - Genes

SN - 2073-4425

IS - 8

M1 - 599

ER -