Trends In Genomic Medicine
Several themes are emerging in the diagnosis and treatment of disease.
(Left) First, as the knowledge of the genomic underpinnings of disease increases, the definition of “self” is likewise expanding. This self includes not just the germline human genome inherited from our parents but also somatic changes in the genomes of tumors, the genomes of commensal microbes that inhabit our body, and the genomes of pathogenic organisms.
Second, the influence of genomics on medicine is moving the diagnosis of diseases toward the earliest possible point in the course of disease, before clinical manifestation.
Third, genomic testing is occurring earlier in the life of a human, moving from adulthood to childhood, the neonatal period, and even prenatally.
(Right) Pharmacogenomic markers are being used in several ways:
• to select targeted therapies exemplified by the breast cancer marker HER-2 and treatment with the monoclonal antibody Herceptin;
• to predict likelihood of response, as in the case of the host IL28B genotype and response to interferon therapy in HCV infection;
• to enhance drug safety, for example, by testing for host HLA genotypes predictive of abacavir hypersensitivity in humans infected with HIV; and
• to optimize dosing of drugs, such as warfarin, based on genotypes indicative of rate of metabolism using, for example, the iWarfarin app.
McCarthy JJ, McLeod HL, Ginsburg GS. Genomic Medicine: A Decade of Successes, Challenges, and Opportunities. Science Translational Medicine 2013;5(189):189sr4. Genomic Medicine: A Decade of Successes, Challenges, and Opportunities
Genomic medicine—an aspirational term 10 years ago—is gaining momentum across the entire clinical continuum from risk assessment in healthy individuals to genome-guided treatment in patients with complex diseases.
We review the latest achievements in genome research and their impact on medicine, primarily in the past decade. In most cases, genomic medicine tools remain in the realm of research, but some tools are crossing over into clinical application, where they have the potential to markedly alter the clinical care of patients.
In this State of the Art Review, we highlight notable examples including the use of next-generation sequencing in cancer pharmacogenomics, in the diagnosis of rare disorders, and in the tracking of infectious disease outbreaks. We also discuss progress in dissecting the molecular basis of common diseases, the role of the host microbiome, the identification of drug response biomarkers, and the repurposing of drugs.
The significant challenges of implementing genomic medicine are examined, along with the innovative solutions being sought. These challenges include the difficulty in establishing clinical validity and utility of tests, how to increase awareness and promote their uptake by clinicians, a changing regulatory and coverage landscape, the need for education, and addressing the ethical aspects of genomics for patients and society.
Finally, we consider the future of genomics in medicine and offer a glimpse of the forces shaping genomic medicine, such as fundamental shifts in how we define disease, how medicine is delivered to patients, and how consumers are managing their own health and affecting change.
