title: Pharmacogenetics of tyrosine kinase inhibitors in gastrointestinal stromal tumor and chronic myeloid leukemia.
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GIST) and chronic myeloid leukemia (CML) are two tumor types deeply different from each other. Despite the differences, these disorders share treatment with tyrosine kinase inhibitor imatinib. Despite the success of imatinib, the response rates vary among different individuals and pharmacogenetics may play an important role in the final clinical outcome.
  
  
  METHODS
  In this review, the authors provide an overview of the pharmacogenetic literature analyzing the role of polymorphisms in both GIST and CML treatment efficacy and toxicity.
  
  
  CONCLUSIONS
  So far, several polymorphisms influencing the pharmacokinetic determinants of imatinib have been identified. However, the data are not yet conclusive enough to translate pharmacogenetic tests in clinical practice. In this context, the major obstacles to pharmacogenetic test validation are represented by the small sample size of most studies, ethnicity and population admixture as confounding source, and uncertainty related to genetic variants analyzed. In conclusion, a combination of different theoretical approaches, experimental model systems and statistical methods is clearly needed, in order to appreciate pharmacogenetics applied to clinical practice in the near future.
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ravegnini
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sammarini
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.affiliation: a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukemia; gastrointestinal stromal tumor; pharmacogenetics; polymorphisms; single nucleotide polymorphism; tyrosine kinase inhibitors