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Current understanding of pharmacogenetic implications of DNA damaging drugs used in osteosarcoma treatment

Claudia Maria Hattinger1, Maria Pia Patrizio1, Silvia Luppi1

  • 1a Pharmacogenomics and Pharmacogenetics Research Unit of the Laboratory of Experimental Oncology , IRCCS Istituto Ortopedico Rizzoli , Bologna , Italy.

Expert Opinion on Drug Metabolism & Toxicology
|March 2, 2019
PubMed
Abstract

Insights

Germline polymorphisms influence high-grade osteosarcoma (HGOS) patient response and toxicity to DNA damaging drugs. Identifying these pharmacogenetic markers can personalize chemotherapy, improving efficacy and safety.

Area of Science:

  • Pharmacogenetics
  • Oncology
  • Genetics

Background:

  • DNA damaging drugs are standard chemotherapy for high-grade osteosarcoma (HGOS).
  • Germline polymorphisms can affect patient susceptibility to adverse events and treatment outcomes.
  • Tumor cell polymorphisms may also impact HGOS prognosis and drug response.

Purpose of the Study:

  • To review pharmacogenetic markers, primarily germline polymorphisms, in HGOS patients.
  • To examine the relationship between these markers and adverse reactions or response to DNA damaging drugs.
  • To discuss concordant and discordant findings across studies.

Main Methods:

  • Literature review focusing on pharmacogenetic markers in HGOS.
  • Analysis of studies investigating germline polymorphisms and their association with drug toxicity and efficacy.
  • Synthesis of existing research on gene variations impacting drug metabolism and DNA repair.

Main Results:

  • Specific germline polymorphisms are linked to varying susceptibility to adverse toxic reactions from DNA damaging drugs.
  • These genetic variations can influence treatment response and prognosis in HGOS patients.
  • Gene variations affect proteins involved in drug uptake, efflux, activation, inactivation, and DNA repair.

Conclusions:

  • Pharmacogenetic markers play a crucial role in predicting response and toxicity to DNA damaging drugs in HGOS.
  • There is a significant need for biomarkers to personalize HGOS therapy.
  • Tailoring treatment based on pharmacogenetics can enhance efficacy and reduce adverse events.
Keywords:
ABC transportersDNA damageDNA repairERCC1GSTdetoxificationgermline polymorphismsosteosarcomapharmacogeneticstoxicity

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