title: FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy.
abstract: While 5-fluorouracil used as single agent in patients with metastatic colorectal cancer has an objective response rate around 20%, the administration of combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5-fluorouracil/folinic acid results in significantly increased response rates and improved survival. However, the side effects of systemic therapy such as myelotoxicity, neurotoxicity or gastrointestinal toxicity may lead to life-threatening complications and have a major impact on the quality of life of the patients. Therefore, biomarkers that would be instrumental in the choice of optimal type, combination and dose of drugs for an individual patient are urgently needed. The efficacy and toxicity of anticancer drugs in tumor cells is determined by the effective concentration in tumor cells, healthy tissues and by the presence and quantity of the drug targets. Enzymes active in drug metabolism and transport represent important determinants of the therapeutic outcome. The aim of this review was to summarize published data on associations of gene and protein expression, and genetic variability of putative biomarkers with response to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5-fluorouracil/leukovorin/irinotecan regimens. Gaps in the knowledge identified by this review may aid the design of future research and clinical trials.
authors.affiliation: Beatrice Mohelnikova-Duchonova, Pavel Soucek, Department of Toxicogenomics, National Institute of Public Health, 10042 Prague, Czech Republic.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mohelnikova-Duchonova
authors.affiliation: Beatrice Mohelnikova-Duchonova, Pavel Soucek, Department of Toxicogenomics, National Institute of Public Health, 10042 Prague, Czech Republic.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.affiliation: Beatrice Mohelnikova-Duchonova, Pavel Soucek, Department of Toxicogenomics, National Institute of Public Health, 10042 Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001711:Biotransformation / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010597:Pharmacogenetics; D010641:Phenotype; D057285:Precision Medicine; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: 5-Fluorouracil; Chemotherapy; Colorectal cancer; Irinotecan; Oxaliplatin