Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.67 (thiopurine methyltransferase)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The great advances in therapeutic success for childhood cancers have provided the impetus for strategies to avoid serious systemic toxicities from chemotherapy. This review describes the impact of genetic mutations in drug metabolism pathways on the toxicity of anticancer agents. Although many polymorphisms have been related to toxicity in adults, these associations are less well defined in children. The role of genetic polymorphisms in MTHFR, TYMS, TPMT, and UGT1A1 in influencing drug toxicity is reviewed. Better understanding of the pharmacogenetic determinants of drug metabolism or pharmacologic cofactors may allow for prospective identification of potential patients who are at increased risk for toxicity, allowing for dose optimization and resulting in a decrease in toxic risk while maximizing efficacy.
 ...
PMID:Pharmacogenetics and pediatric cancer. 1619 21

Multiple drug strategies for many cancer types are now readily available and there is a clear need for tools to inform decision making on therapy selection. Although there is still a long way to go before pharmacogenomics achieves the goal of individualized selection of cancer treatment, promising progress is being made. Genetic testing for thiopurine methyltransferase (TPMT) variant alleles in patients prior to mercaptopurine administration, and for UGT1A1*28 in patients prior to administration of irinotecan therapy, along with the instigation of genotype-guided clinical trials (e.g. TYMS) are important advances in cancer pharmacogenomics. Markers for the toxicity and efficacy of many oncology drugs remain unknown; however, the examples highlighted here suggest progress is being made towards the incorporation of pharmacogenomics into clinical practice in oncology.
 ...
PMID:Impact of pharmacogenomics on clinical practice in oncology. 1739 43

Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations.
 ...
PMID:Pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and ITPA polymorphism. 2352 91