Pharmacogenetics in cancer therapy - 8 years of experience at the Institute for Oncology and Radiology of Serbia

J BUON. 2016 Sept-Oct;21(5):1287-1295.

Abstract

Purpose: Pharmacogenetics is a study of possible mechanism by which an individual's response to drugs is genetically determined by variations in their DNA sequence. The aim of pharmacogenetics is to identify the optimal drug and dose for each individual based on their genetic constitution, i.e. to individualize drug treatment. This leads to achieving the maximal therapeutic response for each patient, while reducing adverse side effects of therapy and the cost of treatment. A centralized pharmacogenetics service was formed at the Institute for Oncology and Radiology of Serbia (IORS) with the aim to provide a personalized approach to cancer treatment of Serbian patients.

Methods: Analyses of KRAS mutations in metastatic colorectal cancer, EGFR mutations in advanced non-small cell lung cancer, CYP2D6 polymorphism in breast cancer, DPD polymorphism in colorectal cancer and MTHFR polymorphism in osteosarcoma have been performed by real time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP).

Results: Mutation testing analyses were successful for 1694 KRAS samples and 1821 EGFR samples, while polymorphism testing was successful for 9 CYP2D6 samples, 65 DPD samples and 35 MTHFR samples.

Conclusions: Pharmacogenetic methods presented in this paper provide cancer patients in Serbia the best possible choice of treatment at the moment.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Biomarkers, Tumor / genetics*
  • Centralized Hospital Services
  • Cytochrome P-450 CYP2D6 / genetics
  • DNA Mutational Analysis
  • ErbB Receptors / genetics
  • Gene Frequency
  • Heterozygote
  • Homozygote
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Pharmacogenetics* / organization & administration
  • Pharmacogenomic Variants*
  • Polymorphism, Genetic
  • Precision Medicine / methods*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Real-Time Polymerase Chain Reaction
  • Serbia
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • KRAS protein, human
  • Cytochrome P-450 CYP2D6
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)