Pharmacogenomics and Pharmacogenetics in Osteosarcoma: Translational Studies and Clinical Impact

Abstract

High-grade osteosarcoma (HGOS) is a very aggressive bone tumor which primarily affects adolescents and young adults. Although not advanced as is the case for other cancers, pharmacogenetic and pharmacogenomic studies applied to HGOS have been providing hope for an improved understanding of the biology and the identification of genetic biomarkers, which may impact on clinical care management. Recent developments of pharmacogenetics and pharmacogenomics in HGOS are expected to: i) highlight genetic events that trigger oncogenesis or which may act as drivers of disease; ii) validate research models that best predict clinical behavior; and iii) indicate genetic biomarkers associated with clinical outcome (in terms of treatment response, survival probability and susceptibility to chemotherapy-related toxicities). The generated body of information may be translated to clinical settings, in order to improve both effectiveness and safety of conventional chemotherapy trials as well as to indicate new tailored treatment strategies. Here, we review and summarize the current scientific evidence for each of the aforementioned issues in view of possible clinical applications.

Keywords: osteosarcoma; pharmacogenetics; pharmacogenomics; tailored treatment; toxicity.

Figure 1

Pharmacogenetic and pharmacogenomic variations impacting on treatment response, outcome and prognosis in high-grade osteosarcoma (HGOS). Genes, polymorphisms and corresponding genotypes (inside parenthesis) are listed inside each box. Genotypes have been reported as they were described in the original studies. Gene polymorphisms or genotypes for which contradictory results have been reported are marked in bold. Genes polymorphisms included in the green boxes (left side) are those which have been indicated to favorably impact on patients’ outcome. Further details, abbreviations legend and references are provided in the text.

Figure 2

Pharmacogenetic variations impacting on chemotherapy-induced toxicities in high-grade osteosarcoma (HGOS). Genes, polymorphisms and corresponding genotypes (inside parenthesis) are listed inside each box. Genotypes have been reported as they were described in the original studies. Genes polymorphisms or genotypes for which contradictory results have been reported are marked in bold. Further details, abbreviations legend and references are provided in the text.