Personalized Medicine for Chronic, Complex Diseases: Chronic Obstructive Pulmonary Disease as an Example

Josiah E Radder; Steven D Shapiro; Annerose Berndt


Personalized Medicine. 2014;11(7):669-679. 

In This Article

The Challenge of Personalized Medicine for Chronic Disease

As the Human Genome Project approached its goal of sequencing the human genome at the beginning of the 21st century, there was significant speculation regarding the impact of this achievement.[1] Some predicted that the results would be immediate, allowing medicine to progress rapidly into a world in which we would have "an intimate knowledge of the propensities of each individual for multifactorial disorders".[2] Others were more circumspect but also perceived that, given time, the genetic code would offer valuable clinical insights into a broad range of diseases.[3]

It was in this context that early adopters of the term 'personalized medicine' began to think about a future in which individual genetic variability, newly available on an unprecedented scale, would affect the way that therapeutics would be designed and applied.[4] Since then, the term has been used broadly to describe medicine that utilizes a range of individual variability – from large 'omics' data to variations of common laboratory measurements – in order to provide better applications and dosing of drugs and improved clinical stratification of patients, as well as to identify biomarkers that indicate susceptibility to or severity of disease. A number of terms have been used to describe this approach, including individualized medicine,[5] network medicine,[6] stratified medicine,[7] precision medicine[8] and P4 medicine: personalized, predictive, preventive and participatory.[9]

Some fields have been more successful than others in utilizing genomic and individual clinical information in order to advance not only research discovery, but also clinical decision-making. In cancer therapeutics, the recognition that many cases of familial hereditary breast cancer can be attributed to mutations in the BRCA1 and BRCA2 genes was a valuable confirmation that certain subtypes of cancers could be clinically managed differently from others.[10,11] Since then, targeted therapies have been developed in order to treat other subsets of breast cancer (e.g., tamoxifen and trastuzumab),[12,13] as well as other cancer types, including chronic myelogenous leukemia (imatinib), gastrointestinal stromal tumors (imatinib),[14] metastatic melanoma (vemurafenib)[15] and non-small-cell lung cancer (gefitinib).[16] Each of these therapies relies on the molecular analysis of the tumor in order to place patients into more individualized treatment groups. Similarly, the field of pharmacogenomics has long been successful in recognizing that not every patient responds to drugs in the same way, and there are currently over 100 US FDA-approved pharmaceuticals that contain pharmacogenomics recommendations in their labeling.[17] A clinically utilized example is HLA typing in order to predict common adverse drug reactions.[18]

In contrast to the fields of pharmacogenomics and cancer therapeutics, relatively few personalized therapies exist for chronic, complex diseases. This is despite WHO statistics that chronic cardiovascular, lung and metabolic diseases are among the top ten killers in the world.[19] Indeed, over 70% of care in the USA today is for chronic diseases, and this will increase as our population ages.[20] Instead, the majority of therapeutics for these diseases utilize a one-size-fits-all approach. It is in part the complexity of these diseases that have made them so difficult to manage in a personalized way. Many chronic diseases are in reality heterogeneous syndromes that have a wide spectrum of clinical manifestations, with the pathogenesis of each presentation attributable to multiple interacting genetic and environmental factors.

In this article, we will describe the current status of personalized medicine for chronic, complex diseases using chronic obstructive pulmonary disease (COPD) as an example. After looking at the genotypic and phenotypic challenges yet to be overcome in COPD, we offer insights into the approaches that we think will further our ability to personalize medicine for this complex disease. We go on to discuss some of the technological tools for both research and clinical purposes that must be improved in order to combine genotype and phenotype and then return these findings to the clinic. Finally, we assert that, for perhaps the first time in history, we have the technology available to begin to bring personalized medicine for chronic, complex diseases to the clinic, but that this will require participation between physicians, researchers, bioinformaticians and providers.