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-χ(2) and log-rank-test, respectively. RESULTS: Patients carrying an ABCG2 -15622T/T genotype or harboring at least one TT 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.
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 NSCLCpatients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-χ(2) and log-rank-test, respectively. RESULTS:Patients carrying an ABCG2 -15622T/T genotype or harboring at least one TT 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.
Authors: George Cusatis; Vanesa Gregorc; Jing Li; Anna Spreafico; Roxann G Ingersoll; Jaap Verweij; Vienna Ludovini; Eugenio Villa; Manuel Hidalgo; Alex Sparreboom; Sharyn D Baker Journal: J Natl Cancer Inst Date: 2006-12-06 Impact factor: 13.506
Authors: Jing Li; George Cusatis; Julie Brahmer; Alex Sparreboom; Robert W Robey; Susan E Bates; Manuel Hidalgo; Sharyn D Baker Journal: Cancer Biol Ther Date: 2007-03-29 Impact factor: 4.742
Authors: Y Ma; S Xin; M Huang; Y Yang; C Zhu; H Zhao; Y Zhang; L Chen; Y Zhao; J Li; W Zhuang; X Zhu; L Zhang; X Wang Journal: Pharmacogenomics J Date: 2016-04-19 Impact factor: 3.550