Thanks to increasing support from the United States government, clinicians, and the pharmaceutical industry, “precision medicine” is the new frontier of healthcare.
In 2015, President Obama launched the Precision Medicine Initiative. This bold new effort provided federal funding to support medical research in the evolving field of personalized treatment and prevention strategies to improve health and treat disease.
The National Institutes of Health (NIH) then formed the Precision Medicine Initiative Working Group. It’s mission: to harness advances in technology, scientific understanding, participant engagement, and to develop a platform for precision medicine research.
What is Precision Medicine?
The term “precision medicine” has become synonymous with personalized or individualized medicine. Physicians have raised the question, “Since when has medicine not been personalized? We treat patients as individuals.”
The NIH defines precision medicine as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.” Traditional approaches to medicine have employed strategies developed for a group of patients with a common clinical presentation. Precision medicine is distinguished as a tailored approach to predict diagnostic, treatment, and prevention strategies for a patient based on an individual’s genetic modifications.1
Today, top healthcare institutions contributing to scientific research proudly display precision medicine divisions and offer precision medicine electives in medical and public health graduate school curriculums. As such, precision medicine can be viewed through three lenses: foundational research, clinical delivery and public health.
Foundational Research GWAS
Foundational research is performed by investigators in close to a dozen categories including genetics, immunology, cell biology, engineering, neuroscience, and stem cells.
Genome-wide association studies (GWAS) are enlisted by geneticists as the key gene discovery mechanism for advancing precision medicine in clinical trials. GWAS generates new and novel information for scientists fueled by large sample sizes. GWAS uses technology to genotype hundreds of thousands of common, single nucleotide polymorphisms (SNPs), which are then analyzed for association with a disease or trait. Some results can be displayed in a graphical representation called a Manhattan plot, which resembles the skyline of the same name.2
AI and Machine Learning
Precision medicine requires an understanding of individual variability, which can only be acquired from obtaining large data sets. As biotechnicians and engineers create algorithms that support machine learning, the volume of data and the complexity of information require new methods in data science, AI, and machine learning crucial for precision medicine development.
The prediction models associated with machine learning and AI aim to provide more precise diagnostics—but still need to be carefully examined to ensure that there is even distribution of gender and underrepresented ethic groups in data collections.
The buzz-worthy phrase these days is moving from the bench to bedside, which includes the application of research to diagnostic and therapeutic interventions in the areas of pediatric oncology, oncology, ophthalmology, neurology, and psychiatry as well as neurodevelopmental, neurodegenerative, and reproductive medicine.
Radiologists play an increasingly important role in precision medicine by further revealing mechanisms and correlations between imaging phenotypes and genomic characteristics. Various oncological and non-oncological disorders—including neurological, rare disease, and even psychiatric disorders—are part of this new paradigm shift. For example, a recent oncological research study in small cell lung cancer reported 89% accuracy of interventional radiology-guided lung biopsies to establish complete tumor molecular profiling.3 This helped to identify the presence of T790 genetic mutation further aiding in treatment and diagnosis. In addition, low-dose CT versus X-ray scans in a small cohort found Stage 1 cancer when there was no evidence on the X-rays.
In addition, radiopharmaceuticals (PET) when taking into consideration the disease stage, provide images of what is occurring inside the body at molecular and cellular levels, further supporting precision medicine advances.4 It is predicted that image-guided biopsies may become the norm in the near future in management of other tumors. This can further reveal reasons why some patients may resist treatment.
Precision medicine approaches to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are now being evaluated through blood-based biomarker development in the prodromal phase, or before clinical symptoms present in patients.
Decades before the first symptoms of Alzheimer’s appear, the brain’s neurons begin to secrete tau proteins, one of the first changes known to occur in the course of the disease. High levels of secreted forms of tau—which can be detected in spinal fluid and in blood—are known to be a highly reliable predictor of who will eventually develop Alzheimer’s disease.5
New biomarker tools can be used to investigate which predisposing genes or comorbid diseases, such as obesity and diabetes, increase the risk of developing neurodegenerative diseases. Research in blood-based biomarkers suggests that if drugs that restore dysfunction rooted in cellular biology can slow Alzheimer’s, those drugs could help a large proportion of patients. In addition, association between biomarker status (amyloid, tau)6 and risk for progression is also part of the complex evaluation of the disease.
Public Health: Contributions and Cautionary Tales
Precision medicine requires an understanding of individual variability, which can only be obtained from large data samples from a diverse population. One highly publicized and continuing effort to expand a public data set is the All of Us research study, which is recruiting one million people to share health information to create a robust data set.
There are a multitude of ethical, cultural, and political questions being addressed by scholars, physicians, and policy makers. For example, genetic counselors have reported that divulging genetic profiles for diseases like breast cancer,7 Huntington’s, Parkinson’s, and Alzheimer’s diseases8 has increased association with suicidality and depression9 in these distinct disease populations.
Researchers also hope to identify specific genomic characteristics and imaging features to predict patient survival. Columbia University has pioneered the study of ethical issues in its Precision Medicine and Society program.
Researchers nationwide have been called upon to develop processes to maximize the safety and effectiveness of disclosing biomarker results to otherwise healthy adults. They endeavor to integrate thoughtful, informed study design, specialized patient resources, as well as emerging experimental and analytic pipelines, for dissemination to the public.
Looking forward, it is exciting to discover that biological functioning characterization efforts in existing biomarker, genetic, neuroimaging, and other resources will provide a comprehensive approach to treating and curing disease. As our understanding of the role of precision medicine rapidly evolves, all of us will play a key role to ensure success.
1.NIH Precision Medicine Initiative. MedlinePlus: the magazine [Internet]. 2015 Fall;10(3):1921. https://www.nlm.nih.gov/medlineplus/magazine/issues/fall15/articles/fall15pg19-21.html. Accessed October 18, 2021.
2.Loos, R. J. 15 years of genome-wide association studies and no signs of slowing down. Nature Communications. 2020; 11(1), 1-3.
3.Giardino A, Gupta S, Olson E, et al. Role of Imaging in the Era of Precision Medicine. Acad Radiol. 2017 May;24(5):639-649.
4.Kreisl W, Kim M, Coughlin J e al. PET imaging of neuroinflammation in neurological disorders. The Lancet Neurology. 2020; 19(11), 940-950
5.Simoes S, Neufeld J, Triana-Baltzer et al. Tau and other proteins found in Alzheimer’s disease spinal fluid are linked to retromer-mediated endosomal traffic in mice and humans. Science translational medicine 2020; 12(571).
6.Papp K , Rentz D, Winski C et al. Associations between biomarker status (amyloid, tau) and risk for progression to MCI/Dementia in the Harvard Aging Brain Study. Talk presented at 2021 Alzheimer’s Association International Conference; July 2, 01 Boulder Colorado.
7.Patenaude F. Young adult daughters of BRCA1/2 positive mothers: What do they know about hereditary cancer and how much do they worry? Psycho-Oncology. 2013; 2024-31.
8.Sexton A, West K, Gil G et al. Suicide in frontotemporal dementia and Huntington disease: analysis of family-reported pedigree data and implications for genetic healthcare for asymptomatic relatives. Psychology & Health: 2020; 1-7.
9.Wilhelm K. Issues concerning feedback about genetic testing and risk of depression. British Journal of Psychiatry. 2009; 194, 404-10, at 407.