A2 Refereed review article in a scientific journal

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




AuthorsReka Varnai, Leena M. Koskinen, Laura E. Mäntylä, Istvan Szabo, Liesel M. FitzGerald, Csilla Sipeky

PublisherMDPI

Publication year2019

JournalGenes

Journal name in sourceGENES

Journal acronymGENES-BASEL

Article numberARTN 599

Volume10

Issue8

Number of pages23

eISSN2073-4425

DOIhttps://doi.org/10.3390/genes10080599

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/42603771


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.

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