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.
Highlights
Prostate cancer (PC) remains the second most common cancer in men, and one of the leading causes of death among Western males [1]
Other drugs have since been developed, some of which are administered in combination regimens with docetaxel, docetaxel remains the main choice of chemotherapeutic agent [4]
None of the variants associated with overall survival (OS) or toxicity had a significant effect on docetaxel pharmacokinetics [27]. These results suggest that variant alleles associated with lowered ABCB1 expression and altered function result in a clinical phenotype of reduced docetaxel efficacy and increased toxicity (TOX) in men with androgen-independent prostate cancer (AIPC)
Summary
Prostate cancer (PC) remains the second most common cancer in men, and one of the leading causes of death among Western males [1]. This is due to the fact that treatment of metastatic prostate cancer (mPC) is becoming increasingly challenging [2,3]. Treatment-associated, germline genomic biomarkers have several advantages: they are static, can be determined, and are robust predictors of drug response/resistance and toxicity. Biomarkers, including somatic genomic alterations, structural variants (e.g., gene fusions, gene rearrangements), splice variants, miRNAs, and differential gene expression, and methylation markers have been shown to modulate docetaxel treatment of PC [8]. The review includes research studies focusing on germline genomic biomarkers, clinical trials designed to incorporate all type of biomarkers, and the implementation of biomarkers in treatment guidelines
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