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Research  |  Major Areas > Personalised Medicine
Personalised Medicine
The aim of personalised medicine or individualised treatment is to match the right drug in the right dose to the right patient and even to design the treatment for a patient according to his/her genotype.  The planning of pharmacogenetic-based tailored drug therapy may involve several steps:
Step 1:
Systematically review all original articles on the impact of drug metabolism enzymes, drug transporters and drug receptors polymorphisms on the metabolism, disposition and effects of the drugs.  Using the knowledge of the population frequencies of the different genotypes and of the pharmacokinetic and pharmacodynamic data derived from these studies, we can calculate the genotype-specific dose requirements for these drugs.
Step2:
The application of genotype-specific dose adjustments for these drugs has to be investigated in prospective clinical trials before decision for introduction into routine clinical practice.
Step 3:
The set up of a personalised medicine center.  Initially, common disorders such as hypertension, hyperlipidaemia and diabetes mellitus should be covered.  Individualised therapy is extended to more complex conditions such as cancers.

Step 4:
Introduction of pharmacogenetic genotyping (PCR-RFLP, PCR-SSCP, ARMS-PCR, gene chip, etc.) into routine clinical practice. Fast and efficient high-throughput genotyping method (e.g. gene chip) will be of great value.
Step 5:
Modify the genotype-based dosing algorithms after reviewing the results and taking into consideration the more recent data.
Examples of Personalised Therapy in Clinical Practice
In cancer chemotherapy of acute lymphocytic leukaemia, administration of drugs such as 6-mercaptopurine and 6-thioguanine can cause severe haematological toxicity or even death in patients possessing nonfunctional variants of thiopurine methyltransferase (TPMT). Genotyping of TPMT can identify those patients who are homozygous for alleles encoding nonfunctional enzyme, and therefore unable to metabolize the drugs to their inactive forms. These patients can be safely treated with doses 10 to 15 times less than commonly prescribed.

Human genetic variability can be expected to affect all treatment modalities. For example, breast cancer treatment with transtuzumab (Herceptin), a humanised monoclonal antibody against the HER2 receptor, is linked to HER2 overexpression which is a marker for responsiveness to transtuzumab therapy.

Warfarin is a widely used oral anticoagulant with a narrow therapeutic index and wide interindividual variation in dose requirement. A large number of pharmacogenetic studies have revealed that genetic polymorphisms in the genes encoding drug-metabolizing enzymes CYP2C9 and the warfarin target protein vitamin K epoxide reductase complex 1 (VKORC1) may affect the response to warfarin. Genetic tests are now available to guide the dosage of warfarin therapy.
 
     
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