Currently, pharmacogenomics is considered as the most promising applied research. It can predict the clinical therapeutic efficacy and toxicity. Recently, studies show that the body disposal process of topoisomerase I inhibitor irinotecan is determined by the pharmacogenetics. And the pharmacogenomics features can predict the risk of serious toxicity on patients. But it can not explain all the reported toxicity or alleviation situation of irinotecan therapy on tumors. In fact, irinotecan price is reasonable and can be accepted by publics. So it has widely application in pharmaceutical field.

An in vitro study finds that the proteins of TOP1, ADPRT, TDP1, CDC45L, NFKB1 and XRCC1 gene encoding can reduce the cytotoxic effects of camptothecin. Researchers though the haplotype retrospective study TOP1 of clear drug targets and downstream effectors of genetic variation affect treatment outcomes with irinotecan program. The relationship between the candidate gene for the common haplotypes and severe adverse reactions and tumor response in patients with advanced colorectal cancer with irinotecan treatment and Sport program. Select from the phylogenetic tree of the haplotypes of each gene in the haplotype of single nucleotide polymorphic markers. Thermal sequencing method for the determination of the patient's DNA haplotype of single nucleotide polymorphism.

The results show that the incidence of TOP1 IVS4 +61 genotype and neutropenia related and TDP1 IVS12 +79 genotype and objective response rate. TOP1 IVS4 +61 AG + GG genotype compared with patients with AA-type survival was significantly prolonged, while the ADPRT +852 (A284A) CT + TT genotype in patients with extended compared with the CC genotype in patients with survival. Compared with other dual-size patients (83%) the treatment of two-body in patients with objective response rate higher. The ADPRT 2/2s genotype severe neutropenia occur than other pairs of size tended to increase. In addition, the study did not find that genetic variation affect the occurrence of diarrhea.

The experiment is the first pharmacogenetics study for irinotecan effect factors. Studies from pharmaceutical raw materials suppliers have shown that the difference between TOP1 and ADPRT may change risk of getting neutropenia on patients. Differences among TOP1, TDP1, ADPRT and XRCC1 may affect the efficacy of platinum-based therapy.Source: