title: Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma.
abstract: Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Claudia Maria
authors.initials: CM
authors.lastname: Hattinger
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tavanti
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Marilù
authors.initials: M
authors.lastname: Fanelli
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vella
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068437:Pemetrexed / Q000009:adverse effects / Q000627:therapeutic use; D010597:Pharmacogenetics; D016597:Trimetrexate / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D000068437:Pemetrexed; D016597:Trimetrexate; D008727:Methotrexate
keywords: Osteosarcoma; methotrexate; pharmacogenetic; pharmacogenomic; toxicity; treatment response