Aims: The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity in non-small-cell lung cancer (NSCLC) patients. Materials & methods: Towards this end, ABCG2 polymorphisms and expression were assessed in DNA and tumors from 94 NSCLC patients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-chi(2) and log-rank-test, respectively. Results: Patients carrying an ABCG2-15622T/T genotype or harboring at least one IT copy in the ABCG2 (1143C/T, -15622C/T) haplotype developed significantly more grade 2/3 diarrhea (p < 0.01). No associations were found between polymorphisms and outcome. Consistently, ABCG2 protein levels in tumors were not significantly different between patients harboring different ABCG2 variants. Conclusion: The ABCG2 -15622C/T polymorphism and ABCG2 (1143C/T, -15622C/T) haplotype resulted in a gefitinib-dependent, moderate-to-severe diarrhea suggesting that these pharmacogenetic markers should be considered to optimize NSCLC treatment.
|Autori:||LEMOS C; GIOVANNETTI E; ZUCALI PA; ASSARAF YG; SCHEFFER GL; VAN DER STRAATEN T; D'INCECCO A; FALCONE A; GUCHELAAR HJ; DANESI R; SANTORO A; GIACCONE G; TIBALDI C; PETERS G|
|Titolo:||Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients|
|Anno del prodotto:||2011|
|Digital Object Identifier (DOI):||10.2217/PGS.10.172|
|Appare nelle tipologie:||1.1 Articolo in rivista|