Pharmacogenetics in the treatment of gastrointestinal stromal tumors–an updated review

Riccardo Ricci, Qianqian Zhang, Gloria Ravegnini, Giorgia Valori, Patrizia Hrelia, Sabrina Angelini

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Introduction: Gastrointestinal stromal tumors (GIST) are the best example of a targeted therapy in solid tumors. The introduction of tyrosine kinase inhibitors (TKIs) deeply improved the prognosis of this tumor. However, a degree of inter-patient variability is still reported in response rates and pharmacogenetics may play an important role in the final clinical outcome. Areas covered: In this review, the authors provide an updated overview of the pharmacogenetic literature analyzing the role of polymorphisms in both GIST treatment efficacy and toxicity. Expert opinion: Besides the primary role of somatic DNA in dictating the clinical response to TKIs, several polymorphisms influencing their pharmacokinetics and pharmacodynamics have been identified as being potentially involved. In the last 10 years, many potential biomarkers have been proposed to predict clinical response and toxicity after TKI administration. However, the evidence is still too limited to promote a clinical translation. To date, the somatic mutational status represents the main player in clinical response to TKIs in GIST treatment; however, pharmacogenetics could still explain the degree of inter-patient variability observed in GIST patients. A combination of different theoretical approaches, experimental model systems, and statistical methods is clearly needed, in order to translate pharmacogenetics to clinical practice in the near future.
Lingua originaleEnglish
pagine (da-a)797-808
Numero di pagine12
RivistaEXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume16
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • Gastrointestinal stromal tumor
  • pharmacogenetics
  • pharmacokinetics
  • polymorphisms
  • tyrosine kinase inhibitors
  • Biomarkers, Tumor
  • Molecular Targeted Therapy
  • Gastrointestinal Stromal Tumors
  • Humans
  • Mutation
  • Pharmacogenetics
  • Prognosis
  • Protein Kinase Inhibitors
  • Gastrointestinal Neoplasms

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