In the mid-1980s, cancer researchers shifted their focus from determining the location of a cancer to identifying the genetic mutations that create it.1 This shift gave birth to a new field of study known as precision medicine, which can now be broadly defined as an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.2 Now, thanks to research in this field, new treatments targeting specific cancer mechanisms are being developed to improve patient outcomes and keep people living longer.
Though the term was coined decades ago, precision medicine gained mainstream prominence in January of 2015 when President Barack Obama announced the Precision Medicine Initiative, which dedicated $215 million of the 2016 presidential budget to investigating research that will “accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.”3 However, some have raised concerns about a lack of clinical diversity on the initiative’s steering panel4,5 and the limited funds allocated to cover a topic that spans a number of different disciplines with costly procedures.6 Even as new technologies have emerged to fulfill the promise of the “1000 dollar genome,” the costs of ordering, processing, and interpreting tests have only risen in recent years.7 Still, diagnostic testing and new treatments have helped to identify new vulnerabilities in diseases such as lung cancer8 and improved outcomes for patients.9
Yet, these advances have also brought new challenges for all health care stakeholders including drug developers, who face increased pressure to bring drugs to market quickly; insurers, who must separate treatments that will help patients from those that will not; patients, whose cost burden and need to stay informed are both growing exponentially; and doctors, who are tasked with understanding an entirely new field they might not be familiar with but is still vital to provide the best possible care for patients.
One of the organizations leading the way in broadening genomic understandings is the Precision Medicine Network. Founded in 2011, the Precision Medicine Network seeks to help lessen the knowledge gap that has resulted due to the rapid pace of discovery and change in cancer diagnosis and care. To learn more about the potential benefits of precision medicine techniques and the work of Precision Medicine Network, Journal of Clinical Pathways spoke with Mark Boguski, MD, PhD, the co-founder and chief medical officer of the organization and a leading expert in precision medicine.
What do you believe is the real potential offered by precision medicine? Have recent advances met your expectations in terms of how successful these methods are proving to be?
I think it’s important to define what we mean when using the term “precision medicine.” I described it in terms of three essential attributes back in 2009.10 Briefly, these are: an understanding of the molecular cause of the disease, the ability to diagnose the specific causal factor, and the ability to treat the root cause specifically and effectively. Precision medicine for cancer has undoubtedly lived up to its potential. Another example of success with precision medicine is in psychiatric disorders, where precision drug selection and dosing can be based on how drug metabolism varies according to a patient’s genes (also known as pharmacogenomics).
What are the major barriers or challenges of precision medicine?
Two major barriers are economics and change management. It’s hard to get people to do things differently from the way they were trained. Motivators for change include better patient outcomes but also the economic incentives of value-based care. A third barrier is lack of training and education in what precision medicine is and how to practice it.
You’ve cited patient access and the need for greater fluency as two consistent issues. How is your organization, Precision Medicine Network, working towards solving these issues? What can institutions do at the clinical level to mitigate these barriers?
We provide a knowledge visualization and decision support platform for precision medicine in oncology. Based on several years of market research, we concluded that patient access to precision medicine was very unevenly distributed and that this was due to a significant knowledge gap between experts at major academic medical centers and physicians at community hospitals where the majority of patients get their care.
You’ve talked before about how the molecular biology of tumors is replacing the tissue of origin as the most important factor in treating cancer. This is especially evident in newer clinical trials in which patients are grouped based on mutation rather than organ system. Is there a concern about whether our health care system will be able to adapt to this change in thinking?
These new clinical trial designs are called “basket” or “umbrella” trials because they place tumors in the same basket (or under the same umbrella) based on molecular commonalities rather than the organ system or tissue of origin of the tumor. The problems will come when these basket trials are translated into basket treatments because oncologists are trained and subspecialize based on the old organ system criteria. Surgical and radiation oncologists won’t be affected as much as medical oncologists and pathologists because their treatments will still be aimed at specific parts of the body. But the latter will have to become molecular “generalists” and applied immunologists, and this will probably require a generational change, starting with reorientation of pathology residency programs and oncology fellowship training.
You’ve spoken a lot about precision diagnostics. How is this different from developing precision treatment regimens for patients? Can you describe how they are intended to be used together?
That’s a good question. Identifying a specific drug target using a precision “companion” diagnostic is an essential step in the process of developing a personalized treatment regimen for a patient. But many other factors also have to be considered in developing an integrated treatment plan, including a patient’s comorbidities, family history, social history, and ease of compliance with treatment. All of these other factors are especially important when managing chronic diseases.
Many are concerned about the potential costs associated with precision medicine initiatives. What do you see as the major challenges for demonstrating the value of precision medicine, in terms of outcomes, toxicity, and costs?
One of the important lessons from a detailed, molecular understanding of the causes and “drivers” of cancer is that, for precision medicine, sometimes doing less will yield more. This management strategy is called treatment de-intensification and can greatly reduce the costs and the likelihood of treatment-related side effects and long-term complications. A proof-of-concept of this strategy is being achieved in head and neck cancers and certain pediatric brain tumors. Based on molecular features, we can identify subsets of these patients for whom less aggressive treatments can improve outcomes and lessen costs. So, precision medicine is not always about developing new “magic bullets” to treat diseases; it is also about stratifying patients who will benefit most from doing less.
Many have suggested that clinical pathways and precision medicine have conflicting goals. Do you agree, or do you think there is potential for precision medicine approaches to be incorporated into pathways?
As I understand it, the main goal of “clinical pathways” is to standardize care to improve outcomes and reduce costs. Precision medicine will allow us, in many cases, to standardize care by identifying which patients are most likely to respond to a specific treatment based on a precision diagnosis of their condition. This process will probably shift some costs from therapeutics to diagnostics, but the hope is that this shift will ultimately lead to overall cost avoidance of administering expensive drugs to patients who are not likely to benefit from them.
References
1. Garraway LA, Lander ES. Lessons from the cancer genome. Cell. 2013;153(1):17-37.
2. About the Precision Medicine Initiative Cohort Program. National Institutes of Health Web site. https://1.usa.gov/1rCYia3. Accessed May 9, 2016.
3. FACT SHEET: President Obama’s Precision Medicine Initiative. The White House Web site. https://1.usa.gov/1T7b7m5. Published January 30, 2015. Accessed May 9, 2016.
4. Katz M. Why the cancer moonshot is already off course. KevinMD Web site. https://bit.ly/1OkmSRV. Published April 25, 2016. Accessed May 9, 2016.
5. Niiler E. Obama’s Anti-Cancer Moonshot Will Need More Than Research. Wired Web site. https://bit.ly/1TzOvrj. Published January 13, 2016. Accessed May 9, 2016.
6. Harris G. $1 Billion Planned for Cancer ‘Moonshot.’ New
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Times. February 1, 2016. https://nyti.ms/24GODkl. Accessed May 9, 2016.
7. Herper M. The $1,000 Genome Arrives – For Real, This Time. Forbes. January 14, 2014. https://onforb.es/1YhWNs5. Accessed May 9, 2016.
8. Politi K, Herbst RS. Lung cancer in the era of precision medicine. Clin Cancer Res. 2015;21(10):2213-2220.
9. Kattan MW, Hess KR, Amin MB, et al. American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine [published online ahead of print January 19, 2016]. CA Cancer J Clin. doi: 10.3322/caac.21339.
10. Boguski MS, Arnaout R, Hill C. Customized care 2020: how medical sequencing and network biology will enable personalized medicine. F1000 Biology Reports. 2009;1:73. doi:10.3410/B1-73.
