Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid tumors.
The validation of predictive biomarkers to tailor chemotherapy is a key issue in the development of effective treatment modalities against cancer. Examples of how genetics might affect drug response are offered by gemcitabine. A substantial number of potential biomarkers for sensitivity or resistance to gemcitabine have been proposed, including ribonucleotide reductase and cytidine deaminase polymorphisms, human equilibrative transporter-1 and ribonucleotide reductase gene-expression and AKT phosphorylation status. These markers displayed a significant relationship with disease response to the drug; however, their robustness needs to be evaluated within prospective studies. Moreover, recent trials of customized chemotherapy based on genetic markers have been carried out in non-small-cell lung cancer and promising pharmacogenetic determinants are gaining momentum, including BRCA1 and ERCC1. Hopefully, biomarkers to select patients most likely to respond to gemcitabine will be validated in the near future.
Danesi
Romano
R
Division of Pharmacology & Chemotherapy, Department of Internal Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. r.danesi@med.unipi.it
Altavilla
Giuseppe
G
Giovannetti
Elisa
E
Rosell
Raffael
R
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring; D006801:Humans; D010597:Pharmacogenetics; D011379:Prognosis; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D000093542:Gemcitabine