The Tailor Made Therapy of Anti-Cancer Drugs

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Anti-cancer drugs have a many serious side effects is well known. There are possible that the gene polymorphisms of drug metabolizing enzymes and drug transporter are affects on the anti-cancer drugs pharmacokinetics, pharmacodynamics and side effects. Further ethnic differences of gene polymorphisms of the several drug metabolizing enzymes and transporter have been reported. Therefore, we investigated that the gene polymorphisms of drug metabolizing enzymes and drug transporter, which are closely related anti-cancer drugs in the Japanese population. Genomic DNA obtained from the non cancer liver tissues by surgical resection for liver disease. Written informed consent was obtained from 34 patients with liver disease. This study was approved by the ethics committee of St. Marianna University School of Medicine. We can identified gene polymorphisms of CYP's (CYP1A2*1F, CYP2C19*2, *3, CYP2D6*4, *5, *6, *10, CYP3A4*4, *16) and MDR1 (-41A/G, -129T/C, 1236T/C, 2677G/A, T, 3435C/T, 4036A/G). The allele frequencies of CYP's were (CYP1A2*1F(69.4%), CYP2C19*2, *3(41.7%), CYP2D6*4, *5, *6, *10(42.6%), CYP3A4*4, *16(2.9%)), and MDR1 were (-41A/G(16.7%), -129T/C(9.4%), 1236T/C(24.2%), 2677G/A, T(64.6%), 3435C/T(40.9%), 4036A/G(27.3%)), respectively. The allele frequencies of CYP1A2, CYP2C19, CYP2D6, and 12677G/A, T, and 3435C/Tof MDR-1 were shown to be high compared to previously reports. These result indicated that the needs for attention on the using drugs for metabolism by these CYP's and for transport by MDR-1. These data suggested that the pharmacogenomic data is available on the tailor made therapeutic strategy of patients having above gene polymorphisms in Japanese.