Pharmacogenetics: Where Is It Headed?
When Will Pharmacogenetics Revolutionize Drug Therapy?
When the Human Genome Project (HGP) was completed in 2001, it was anticipated that within the ensuing 10 years, (ie, by 2011) genetic information would lead to advances in targeted drug discovery and prediction of drug responsiveness, and that by 2020, the pharmacogenomics approach for predicting drug responsiveness would become standard practice.1
A recent article, "Pharmacogenetics in Clinical Practice: How Far Have We Come, and Where Are We Going?" analyzes how close we are to fulfilling these expectations.1
Genetic-Guided Drug Discovery and Development
There have been "notable advances in the use of genomic information to guide drug discovery and development, particularly in the area of cancer," as well as two additional drugs (one for CCR5-tropic HIV and one for cystic fibrosis patients with the CFTRG551D mutation).1
The author suggests that drugs to treat cancer and infectious diseases may represent the "low-hanging fruit for genetically informed drug discovery," as most of these drugs are highly focused on targeted mechanisms, further aided by genomics and systems biology approaches.2
By contrast, common, complex diseases have "environmental and multiple genetic influences, with each gene contributing in smaller ways." Thus, the author notes, the targeted approach focusing on specific mutations may be less suited for chronic disease treatments.
However, genes identified through genome-wide association may still identify important protein targets. For example, polymorphisms in CETP and PCSK9 are associated with elevated high-density lipoprotein (HDL) and low levels of low-density lipoprotein (LDL) respectively.3,4 Drugs targeting these proteins (rather than the genetic polymorphisms) are promising agents in potentially raising HDL and lowering LDL.5,6
The author suggests that "the next decade will provide clarity about whether genetic/genomic-guided approaches to drug discovery and development will largely remain within therapies for cancer and infectious diseases, or will also become a common, widespread approach to the development of drugs for common diseases."
Pharmacogenetics to Guide Drug Therapy Decisions in the Clinical Setting
There have been substantial advances in discoveries of genetic associations with drug response.1 The U.S. Food and Drug Administration (FDA) has been aggressive in providing genetic labeling on new drugs,1 and the Clinical Pharmacogenic Implementation Consortium (CPIC), formed in 2009, provides comprehensive reviews and guidelines on the clinical use of pharmacogenetics information. Eight currently published guidelines focus on commonly used agents such as clopidogrel7 or codeine.8