Advances in Personalized Medicine

Personalized medicine is common in oncology practice today, where the features of the patient’s genome are taken into account to determine what treatments are most likely to be effective. The ability to correlate genetic or molecular features of a cancer to the effectiveness of different chemotherapy regimens has led to increased survival rates.

Advances in genome sequencing have allowed this same principle to be applied to the study of proteins, metabolic pathways, and the processing of specific compounds, all of which vary between individuals. Genome-wide association studies (GWAS) compare groups of people with a certain disease or trait to people without it to identify genetic variations that are more prevalent compared to the control group. This can show which genes are associated with an increased risk of particular diseases, or with adverse reactions to some drugs1. For instance:

  • Certain single nucleotide polymorphisms (SNPs) have been associated with variations in response to a particular treatment for genotype 1 hepatitis C2.
  • Genetic variants in cytochrome P450 enzymes have been shown to affect the metabolism of certain drugs, among them many of the most commonly used antipsychotics3.
  • Variations in the enzyme butyrylcholinesterase have an impact on the half-lives of isoniazid, procainamide, and suxamethonium chloride, with consequences for their efficacy and duration4.
  • Differences in the metabolism of thiopurines can lead to bone marrow suppression, and patients with a genetic deficiency of thiopurine methyltransferase (TPMT) require only 6-10% of the standard dose5.
  • The CYP2C19 gene is linked to an inability to metabolize the antiplatelet agent clopidogrel; this deficiency can lead to heart attacks or sudden death due to clots following the placing of a coronary stent6.
  • Depending on the patient’s genotype, vitamin E can either raise or lower the risk of cardiovascular disease in diabetics7.

The traditional, one-size-fits-all approach to treatment disregards these important variations, with dangerous consequences for some patients. Personalized medicine aims to remove this element of unpredictability by identifying the determinants of individuals’ varying responses, allowing patients to accurately receive treatments that work for them and to avoid those that are useless or worse.

1. Pearson TA, Manolio TA (March 2008). "How to interpret a genome-wide association study". JAMA 299 (11): 1335–44.
2. Ge D et al. (September 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature 461 (7262): 399–401.
3. Cichon S, Nöthen MM, Rietschel M, Propping P (2000). "Pharmacogenetics of schizophrenia". Am. J. Med. Genet.
4. Gardiner SJ, Begg EJ (September 2006). "Pharmacogenetics, drug-metabolizing enzymes, and clinical practice". Pharmacol. Rev. 58 (3): 521–90.
5. Genetic Science Learning Center. "Your Doctor's New Genetic Tools.". Lern.Genetics. Retrieved 15 April 2012.
6. Shuldiner AR et al. (August 2009). "Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy". JAMA 302 (8): 849–57.
7. Farbstein D et al. (November 2011). "Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype". Atherosclerosis 219 (1): 240–4.