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Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma

Claudia Maria Hattinger1, Elisa Tavanti1, Marilù Fanelli1

  • 1a Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology , Orthopaedic Rizzoli Institute , Bologna , Italy.

Expert Opinion on Drug Metabolism & Toxicology
|October 21, 2016
PubMed
Abstract

Insights

Pharmacogenomic biomarkers can predict how high-grade osteosarcoma patients respond to antifolate drugs like methotrexate. Identifying these genetic markers may personalize future cancer treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Drug Metabolism

Background:

  • Antifolates, including methotrexate (MTX), are established antitumor agents used for high-grade osteosarcoma (HGOS).
  • Limited efficacy and variable toxicity are observed with antifolates in HGOS patients.
  • Existing antifolates like trimetrexate and pemetrexed show modest activity in recurrent HGOS.

Purpose of the Study:

  • To summarize existing pharmacogenomic data for genes influencing antifolate metabolism, transport, and MTX toxicity in HGOS.
  • To explore the potential of genetic biomarkers for optimizing antifolate therapy in HGOS.

Main Methods:

  • Review of published pharmacogenomic studies related to antifolate treatment in HGOS.
  • Analysis of genetic variations affecting antifolate pathways and MTX-related adverse events.

Main Results:

  • Evidence suggests patient response and toxicity to antifolates vary significantly.
  • Specific genes involved in antifolate metabolism and transport are linked to treatment outcomes.
  • Genetic factors influence susceptibility to MTX-related toxicities in HGOS.

Conclusions:

  • Pharmacogenomic insights are crucial for understanding differential responses to antifolates in HGOS.
  • Genetic biomarkers hold promise for tailoring antifolate treatment strategies.
  • Future personalized medicine approaches in HGOS may leverage pharmacogenetic profiles.
Keywords:
Osteosarcomamethotrexatepharmacogeneticpharmacogenomictoxicitytreatment response

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