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Making Medicine Personal

Thanks to precision medicine, medical care is getting personal — highly personal. Described as the future of medicine, precision medicine technologies enable doctors and researchers to analyze what a person’s genes say about them and how that relates to a specific diagnosis. The intention is that precision medicine can provide more accurate care, especially when it comes to cancers, COVID-19, and other rare disorders.

One leader in the field of precision medicine is David C. Fajgenbaum, M.D., MBA, MSc. Dr. Fajgenbaum is an associate professor of medicine in translational medicine and human genetics at the University of Pennsylvania. He is also the founding director of the Center for Cytokine Storm Treatment and Laboratory (CSTL), which aims to identify and treat patients with Castleman disease, COVID-19, and other cytokine storm disorders. CSTL works to uncover “novel diagnostic biomarkers and therapeutics, identify optimal treatment approaches, and to provide world-class patient care,” as noted on med.upenn.edu/CSTL.

Fajgenbaum and his fellow researchers at CSTL view precision medicine technology as central to their work. By examining how the specific genes in a person’s makeup correlate and relate to a diagnosed or undiagnosed illness, physicians can determine the best course of action.

A genetic profile may be produced by checking for biomarkers. A biomarker is a measurement of what is happening in an organism or cell at any given moment. This could include having your blood or urine tested or a doctor sampling a piece of tissue during a biopsy. Biomarkers have even more roles to play in the application of precision medicine. Not only can they be used for diagnostic purposes, but they are also helpful for prognostic and therapeutic support. Specifically, prognostic assessments will aid in predicting a patient’s outcome and therapeutic biomarkers will potentially predict how a patient will respond to any given treatment.

David Fajgenbaum draws upon his own experience as a Castleman disease patient to help others cure their own. (Photo courtesy of Perelman School of Medicine, Office of David Fajgenbaum)

CSTL is dedicated to the discovery of new uses for existing drugs that can save people’s lives. This issue hits particularly close to home for Fajgenbaum, who literally saved his own life through diagnostic research. A former Georgetown University football player, Fajgenbaum was a walking health advertisement. He was a regular at the gym, even during his time in medical school at UPenn. However, in 2010 his body started to betray him, and his fellow doctors had no clear perspective on what exactly was going wrong. With swollen lymph nodes, his organs straining to continue, brain fog, and severe exhaustion, Fajgenbaum endured multiple rounds of chemotherapy, which weakened him further. Eventually a sample of his lymph node was sent to the Mayo Clinic, and they determined it was Castleman disease, a rare disease that acts like a cross between cancer and an autoimmune disorder.

Even with the Castleman disease diagnosis, it was unclear how Fajgenbaum would fight and beat the illness.

“I became ill with idiopathic multicentric Castleman disease when I was a third-year medical student at UPenn,” says Fajgenbaum. “After nearly dying five times in three years, I performed experiments on my own blood samples to dissect what was going wrong in my immune system. I discovered that an important communication line called mTOR seemed to be in overdrive and began testing an FDA-approved mTOR inhibitor on myself for the first time ever for my disease. I’ve been in remission for over nine years. This is an example of truly personalized, precision medicine. Since launching my Center for Cytokine Storm Treatment and Laboratory, we’ve repeated this precision medicine approach several times, identifying mechanisms underlying disease processes and then repurposing existing drugs from other drugs to treat them.”

The University of Pennsylvania Perelman School of Medicine research building in Philadelphia. (Shutterstock.com)

After graduating from medical school, Fajgenbaum entered UPenn’s Wharton School with the intention of continuing to study how better to identify and treat other people with rare diseases. He founded the Castleman Disease Collaborative Network (CDCN), where he initiated a novel “collaborative network approach.” Not only does the CDCN research new ways to use the 1,500 already existing FDA approved drugs to treat the 7,000 rare diseases with no known treatment options (or very few), the CDCN encourages patients to submit their anonymous blood samples and medical data to fight for better patient care. Patients can join the fight at cdcn.org.

Fajgenbaum says that precision medicine is now being used across all of Penn Medicine.

David Fajgenbaum is always chasing the cure at the Castleman Disease Research Program at Penn. (Photo courtesy of Perelman School of Medicine, Office of David Fajgenbaum)

“Over 10 years ago, Penn Medicine began utilizing precision medicine in oncology,” he says. “Specifically, we would perform genetic testing of patients’ cancers to determine the precise genetic issues driving the cancers in those patients so a precise/targeted therapy could be used. Now, we’re seeing it across Penn Medicine. We’ve seen the adoption of genetic testing to predict which patients are likely to experience a medication side effect in many areas outside of cancer. In the center that I lead at Penn [Center for Cytokine Storm Treatment and Laboratory], we are performing deep immune profiling of patient samples to understand perturbations that can potentially be treated with existing drugs approved for other diseases.”

The U.S. Food and Drug Administration (FDA) is currently exploring new ways to advance breakthroughs in diagnosis, prognosis, and treatment of diseases. Their cloud-based sharing portal precisionFDA, at precision.fda.gov, is “a secure, collaborative, high-performance computing platform that builds a community of experts around the analysis of biological datasets in order to advance precision medicine.”

Since the growing success of precision medicine treatments, the FDA has approved several new cancer treatments associated with genetic and molecular changes. These include Crizotinib (Xalkori) for patients with non-small cell lung cancer that contains a mutation in the ROS or ALK genes; Dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with melanoma containing a specific mutation in the BRAF gene; Imatinib (Gleevec) for patients with chronic myelogenous leukemia (CML) that contains a genetic abnormality called the “Philadelphia chromosome”; and Trastuzumab (Herceptin) for patients with breast cancer that produces high levels of a protein called HER2 (fda.gov).

While health care is undoubtedly expensive, precision medicine technology could potentially reduce medical costs since it is easier to avoid care or pharmaceuticals that are unlikely to work or will make you ill (such as unwanted side effects). Conversely, genetic testing will involve gene or protein testing that may not be covered by everyone’s health insurance. In addition, those who have a heightened risk of cancer due to family history might undergo numerous genetic tests, which are also expensive.

The Penn Center for Personalized Diagnostics (CPD) is a joint initiative between Penn Medicine’s Department of Pathology and Laboratory Medicine and the Abramson Cancer Center to support precision medicine at Penn. CPD provides the highest volume of genome testing in the region. Patient care is centered around personalized treatment options that are all based on genetic testing. There is also a great emphasis placed on avoiding treatments that are excessively harsh or aggressive. CPD is led by a team of molecular geneticists, researchers, and physicians. All the data compiled at CPD is shared with the patient’s physician so that individualized patient care is of the utmost practice and concern.

The Basser Center for BRCA at Penn Medicine’s Abramson Cancer Center signifies a collaboration between scientists, geneticists, physicians, and genetic counselors. The Basser Center recently celebrated its 10th anniversary as a leading treatment center for BRCA-related research, education, and cancer treatment. The Basser Center offers detailed genetic testing and counseling, both of which are key to treating BRCA-related cancer risks. For those who are interested in meeting with a genetic counselor at Penn Medicine and how to be evaluated for BRCA testing, contact the MacDonald Cancer Risk Evaluation Center at 215.349.9093 or visit basser.org/genetic-testing-resources.

When asked how the technology behind precision medicine for the treatment of cancer and other illnesses may advance in the near future, Fajgenbaum says, “The sequencing technology that enables precision medicine is becoming less expensive and much faster, so we’ll see more breakthroughs and more examples of precision medicine in practice at Penn Medicine.”

RWJBarnabas Health has numerous cancer treatment centers throughout Central New Jersey where precision medicine treatment is offered. By closely examining the evolution of each patient’s cancer cells, it aims to recommend the most effective treatments for cancer remission and recovery. These may include surgery, chemotherapy, radiation therapy, immunotherapy, and clinical trials. Precision medicine may also include further individualized treatment such as a unique combination of cancer care.

Rutgers Cancer Institute of New Jersey received the state’s highest score in cancer specialty by U.S. News and World Report in July 2022. A RWJBarnabas Health hospital, Robert Wood Johnson University Hospital serves as the primary teaching hospital for Rutgers Robert Wood Johnson Medical School and the flagship Cancer Hospital of Rutgers Cancer Institute of New Jersey. RWJBarnabas Health will continue to expand in 2024 with the opening of the Jack and Sheryl Morris Cancer Center, which will be New Jersey’s only freestanding cancer hospital.

Blue helix human DNA structure

Human DNA structure. (Shutterstock.com)

Dr. Shridar Ganesan co-leads Rutgers Cancer Institute’s Clinical Investigations and Precision Therapeutics Program and is currently exploring how DNA repair defects in cancer can be exploited to develop novel effective treatments. Ganesan is the principal investigator of a clinical trial that uses DNA analysis of rare and resistant cancers to apply next-generation sequencing technology to identify how best to treat them.

Ganesan explains, “In recent years we have learned that cancers that arise in one organ, such as breast cancer or lung cancer, are not just one disease, but rather a collection of distinct diseases with varying responses to different treatment strategies. We therefore need to examine many features of each cancer to better classify it and identify effective treatment.” (cinj.org).

Monmouth Medical Center’s Southern Campus in Lakewood now uses a landmark tumor profiling system to closely examine genetic cancer growth. With tumor profiling, doctors send a sample of the tumor to a lab to be analyzed for biomarkers. Dr. Seth Cohen stated, “In the old days, we just gave a report saying there is a cancer. It’s better to say, ‘this is a cancer, this gene is promoting this cancer, and if you use this drug for that gene, you could have a great impact on a person’s life.’ Patients are living longer because these targeted drugs are out there.” (rwjbh.org).

Cohen says the treatment of lung cancer has changed in many ways. “The way we treat lung cancer today is not just by knowing it’s a lung cancer,” he says. “We treat lung cancer by knowing about the genetic profile of that lung cancer.” (rwjbh.org).

Thus, by knowing a tumor’s genetic profile, the cancer treatment and protocol is much more effective. Many patients also have the bonus of feeling better taken care of and understood thanks to their physician’s tailored approach.

Finally, while not all cancers are alike, and no two people are the same, it appears that precision medicine may offer a hopeful new way to treat afflictions that used to be handled in a one-size-fits-all approach. In fact, advancements in gene sequencing, data analysis, and genomic medicine means that precision medicine may soon be increasingly applied to even more diseases.

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