title: A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review.
abstract: OBJECTIVE
  The individual response to targeted tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell cancer (mRCC) is highly variable. Outlined in this article are findings on potential biomarkers for TKI treatment outcome in mRCC and an evaluation of the status of clinical implementation.
  
  
  METHODS
  Articles were selected by two independent reviewers using a systematic search in five medical databases on renal cell carcinoma, TKIs, and pharmacogenetics.
  
  
  RESULTS
  Many researchers have focused on predictive biomarkers for treatment outcome of targeted therapies in mRCC patients. Attempts to explain differences in efficacy and toxicity of TKIs by use of genetic variants in genes related to the pharmacokinetics and pharmacodynamics of the drug have been successful.
  
  
  CONCLUSIONS
  Most findings on potential biomarkers have not been validated and therefore biomarker testing to guide choice of therapy and dose in mRCC is not yet feasible.
authors.affiliation: a Department of Clinical Pharmacy and Toxicology , Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Meta H M
authors.initials: MH
authors.lastname: Diekstra
authors.affiliation: a Department of Clinical Pharmacy and Toxicology , Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Swen
authors.affiliation: b Department of Medical Oncology , Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: a Department of Clinical Pharmacy and Toxicology , Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010597:Pharmacogenetics; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib
keywords: biomarker; efficacy; metastatic renal cell cancer; pharmacogenetics; pharmacogenomics; single nucleotide polymorphism; toxicity; tyrosine kinase inhibitor