Figure 1. Metabolic Genes. Variation in the Cytochrome P450 metabolic genes can lead to higher or lower concentrations of drugs. Since recommended dosing assumes normal metabolism, individuals with genetic variants that impact drug metabolism may require dose adjustments or, in some cases, should avoid drugs impacted by genetic variants.
Figure 2. Normal metabolic genes result in effective drug therapy
Tus, these technologies are becoming af- fordable to not only high profile individu- als such as Steve Jobs and author Christo- pher Hitchens, but to the average citizen. Tese men notably had their genomes and the genomes of their tumor cells sequenced to look for differences between the two in order to choose the correct treatment. Unfortunately they lost their batles with cancer, but the approach is a very rational one that will likely become the norm. Leukemia researcher Dr. Lukas Wartman is a success story, where RNA se- quencing of his own leukemia cancer cells revealed an overabundance of a particular receptor tyrosine kinase (RTK) that was fueling the cancer’s growth. Dr. Wartman was able to use this information to choose an available cancer medicine that targeted that RTK, but his insurance would not pay because that drug was for pancreatic can- cer, not leukemia. He scraped together the money to pay for the drug and survived, but this points out the clash between the old way of thinking, that is, one-drug-fits- all, and the new way, which is a personal- ized medicine approach. Cancer is not the only disease where
genotyping is of great benefit. In fact, mainstream genotyping has to the pres- ent day mainly focused on drug metabo- lizing enzymes such as the cytochrome P450 super family of enzymes, which metabolize the vast majority of presently prescribed drugs. SNPs in these CYP enzymes greatly influence the blood levels of the active form of prescribed drugs, and contribute to over- and under- dosing. In the case of Plavix for example, variations in the CYP2C19 gene affect the metabolic conversion of this inactive pro-drug into its active form. Genotyp- ing CYP2C19 for each patient requir- ing Plavix ensures an optimal dosage is prescribed. Likewise, variations in the CYP2D6 gene affect the efficacy of many different types of drugs, as CYP2D6 acts
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