Personalized Medicine

December, 2011

In recent months, a number of us have had several opportunities to talk with alumni and friends of Penn State Hershey Medical Center and College of Medicine about the promise of personalized medicine. These discussions have generated great excitement and enthusiasm for this new area of medicine, which embodies the close connection between research discoveries and clinical progress that we are fostering through translational research. As members of our Penn State Hershey community, we hope you will also be excited about the potential of personalized medicine and what it means for our institution, as well as for the patients we serve.

So what exactly is personalized medicine? It is an approach to tailoring medicine and health care to the individual, based on a number of factors – genetic, genomic, environmental, and behavioral – that affect an individual's health. Personalized medicine recognizes that many diseases are expressed differently in each patient. Understanding how these individual variations affect the course of disease and in response to treatment can be important in developing more effective therapies. But personalized medicine isn't just about treating disease – it's also a way to enhance prevention and early diagnosis, tailoring strategies for maintaining good health to an individual's risk factors and needs.

One term frequently mentioned in discussions of personalized medicine is genomics. While the field of genetics studies the inheritance of individual genes and the traits – including diseases – linked to them, the newer field of genomics is the study of all of an individual's genes and the ways in which they interact with each other and with the individual's environment and health behaviors. More and more, we are finding that these gene-gene and gene-environment interactions are crucial to understanding why some individuals develop a particular disease when others don't, and why treatments that help some people are ineffective, or even harmful, in others suffering from the same disease. According to the Centers for Disease Control and Prevention, genetic factors play a role in many of the leading causes of illness, disability, and death in the United States – including familiar diseases like cancer, heart disease, diabetes, mental illness, autism, and Alzheimer's disease. Personalized medicine thus offers an opportunity to address many of the most devastating and costly health problems affecting our population.

Incredible as it may seem, it has been nearly a decade since the sequencing of the human genome was completed. Personalized medicine represents the next leap forward in medicine and is the result of this groundbreaking work. This emerging field not only dramatically changes our knowledge and understanding of human health and disease, but also offers many possibilities for improving the health of individuals. Improved medical decision-making, based on a better understanding of individual risks and benefits, will lead to better health outcomes for many patients. Personalized medicine also offers the potential to tailor therapies to the individual, so that each patient receives the treatment that will work best for him or her, at the right time and in the right dose.

A personalized approach enables doctors and patients to choose the therapies that are most likely to be beneficial to each patient, and to identify which approaches are likely to be ineffective. At the macro level, this leads to greater efficiency and potential cost savings in health care. For the patient, this may mean more timely and effective treatments. Some familiar examples of personalized medicine as it is commonly applied include close monitoring of patients who test positive for cancer-related genes, tumor-typing in breast cancer patients to determine if the disease will respond to standard chemotherapy or newer agents, and genetic testing to determine the dosage of the blood thinner Coumadin, based on individual differences in how the drug is metabolized.

We are poised to play a leading role in the emerging field of personalized medicine. Numerous members of our faculty are already making exciting contributions to personalized medicine, and we are continuing to build capacity and recruit additional scientists in areas such as genomics. Our researchers working in this field are building on a foundation laid by one of our eminent founding faculty members who is an early pioneer in personalized medicine. Dr. Elliot Vesell, Evan Pugh professor emeritus and founding chair of the Department of Pharmacology, played a critical role in establishing the fields of pharmacogenetics and pharmacogenomics. His groundbreaking research has identified many factors, both environmental and genetic, that cause large variations in how individuals respond to drugs. At the same time, he developed new methodologies for investigating variations in drug response. Though retired, Dr. Vesell remains an active scholar and continues to collaborate with faculty in the Department of Pharmacology, which continues to have a strong emphasis in pharmacogenetics and pharmacogenomics.

Research in personalized medicine is not limited to pharmacology. Across Penn State Hershey, scientists and clinicians are using the tools of personalized medicine to benefit our patients. Dr. Wafik El-Deiry, Rose Dunlap Division Chair of Hematology/Oncology and Associate Director for Translational Research, Penn State Hershey Cancer Institute, is leading efforts to apply personalized medicine to cancer diagnostics and therapeutics. Working on a variety of cancer types including breast and colorectal cancer, Dr. El-Deiry and his colleagues are exploring variations in tumor biology and cell death pathways involved in tumor suppression, leading to more tailored approaches to treatment. In addition to studying how and why tumor cells respond to chemotherapy and other agents, Dr. El-Deiry’s research also examines why tumors become resistant to certain treatments and how to develop ways to reverse that resistance. In the Department of Public Health Sciences, assistant professor Dr. Carla Gallagher and her colleagues are studying how genetic variation contributes to cancer risk, including susceptibility to the carcinogens from smoking, diet, and the environment. This research suggests possible ways to identify individuals at greater-than-average risk for developing cancer, who can then benefit from more aggressive monitoring to detect cancer early, and who will also benefit most from eliminating carcinogens such as tobacco smoke. Dr. Gallagher’s research also examines the genetic underpinnings of variations in response to cancer therapeutic agents, an important factor in determining the appropriate dosage for individual patients. Dr. El-Deiry, Dr. Gallagher, and many other faculty across our campus are collaborating with colleagues in our pharmacogenetics program, based in the Department of Pharmacology and directed by Dr. Philip Lazarus.

Personalized medicine at Penn State Hershey is by no means limited to cancer. Our researchers are identifying the ways in which personalized approaches can address a wide range of physical and behavioral health issues. In the Department of Cellular and Molecular Physiology, Dr. Sean Stocker is developing methods for measuring sympathetic nerve activity – which, in excess, is linked to certain forms of cardiovascular disease. His group is using these new approaches to understand how the central nervous system detects changes in dietary sodium differently between salt-resistant and salt-sensitive subjects and help guide the development of new drugs. Dr. Sue Grigson, Professor of Neural and Behavioral Sciences, is expanding our knowledge of the mechanisms underlying addiction. Understanding the variations in how individuals’ brains respond to perceptions of risk and reward can lead to more effective approaches to preventing and treating addiction. Ultimately, such research will result in better health for individuals suffering from addiction and give us new tools to address this important public health and social issue. Research conducted by Dr. Daniel Notterman, Vice Dean for Research and Graduate Studies and Professor of Pediatrics and Biochemistry and Molecular Biology, has demonstrated the importance of gene-environment interactions in women’s risk of post-partum depression (PPD), as well as the complexity of those interactions. Dr. Notterman and his collaborators have shown that women with a genetic propensity to react more strongly to environmental stress develop PPD at a higher rate in a poor environment, but have better-than-average outcomes in a rich environment. This more sophisticated understanding of the interplay between genetic and environmental risk factors for PPD can ultimately lead to more effective screening and early intervention.

These are just a few examples of the exciting ways in which personalized medicine is changing the science and practice of medicine. There are many more, and our activity in this area will continue to grow. The Penn State Clinical and Translational Science Institute now provides a valuable framework for the clinical research that will be vital to the growth of personalized medicine at our institution. Our investment in electronic health records and health informatics supports our ability to customize preventative and therapeutic care to the individual patient, as well as our capacity for clinical research. Our new incoming chair of the Department of Biochemistry and Molecular Biology, Dr. James Broach, is an internationally-renowned figure in genomics research at Princeton University who will further add to our strength in this area.

For personalized medicine to succeed in transforming health care, we must do more than simply advance our understanding of disease and translate that understanding into improved clinical practice. There are also ethical issues to be addressed, such as the privacy concerns that can arise around genetic testing, and concerns about the potential for discrimination or denial of care on the basis of the very same factors that identify disease risk. As we expand the science of personalized medicine, we must ensure that these issues are addressed so that patients can fully benefit from the promise of this new frontier in medicine.

The potential benefits of personalized medicine transcend our four-part mission of education, research, patient care and community service. While we are still in the early stages of our efforts in this new emerging field, it offers tremendous promise for our institution and all those whom we serve.

 

Harold L. Paz, M.D.
Chief Executive Officer, Penn State Hershey Medical Center
Senior Vice President for Health Affairs, Penn State
Dean, Penn State College of Medicine