ReviewThe path to personalized medicine
Introduction
The realization of personalized medicine, or the fine tailoring of the practice of medicine to an individual, is being fostered through numerous efforts aimed at characterizing individual differences in molecular processes underlying disease pathogenesis, disease progression and the response to therapeutics. Once these molecular differences are understood, therapeutic development will be enhanced by using the information to identify individuals more likely to benefit from a given intervention strategy. High-throughput genomic technologies are already providing the data that will serve as the foundation of personalized medicine. Here, we briefly describe the current state of those technologies and highlight the directions required to fully develop and integrate personalized medicine into practice. We draw upon a range of examples that demonstrate the relevance of molecular markers throughout the development and treatment of disease, including markers for disease predisposition, screening and progression, as well as markers for drug response and drug monitoring (Fig. 1).
Section snippets
Individual differences in the development of disease and response to therapeutics
Clearly, for many common diseases, there is abundant evidence to suggest that the molecular underpinnings of disease susceptibility, and its natural history, differ markedly among individuals. For example, while it has been demonstrated in numerous investigations that the development of obesity, asthma, type 2 diabetes and cardiovascular disease are under genetic control 1., 2., 3., 4., there is no evidence to suggest that the genetic basis is due to variation in just a single gene. Instead,
Technological advances drive broad biomarker discovery
While the existence of individual differences in disease predisposition, progression and response to therapeutics is far from a novel concept, our ability to comprehensively measure the molecular markers that track these processes, and draw proper inferences from large amounts of molecular data, is novel. Over the past decade, significant advancements have been made in technologies to discover variation at the mRNA, DNA and protein levels. Indeed, with the advent of glass and nylon microarray
The predictive value of biomarkers
The impact that advanced genomic technologies and carefully designed biomarker studies will have on the personalization of medicine is foreshadowed in the current literature. For example, Mallal et al. [13•] conducted a pharmacogenetic investigation (i.e. a genetic study of drug response) of abacavir, an HIV-1 nucleoside reverse transcriptase inhibitor. They implicated MHC alleles that predict response to hypersensitivity among 5% of the HIV cases receiving the drug. Their findings suggest that
Turning biomarker discoveries into personalized medicines
All of the examples cited above provide excellent demonstrations of the power of new technologies to deliver a range of biomarkers that index individual differences in disease predisposition, progression and response to therapeutics. Thus, they clearly form a basis for the ‘personalization’ of medicine. However, the discovery of these markers is not sufficient for the pharmaceutical industry to deliver personalized medicines. Indeed, the delivery of such medicines will require the careful
Conclusions
Clearly, several challenges remain to achieve a successful integration of large-scale, biomarker studies with drug development. While there has been an incredible advance in high-throughput, molecular technologies, over the past several years, further improvements in technologies and validation strategies are required to capture the true extent of individual differences in molecular markers. For example, although it is plausible to consider screening the genome for SNPs or haplotypes that
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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