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Precision medicine, which leverages the genetic and genomic features that contribute to the development of cancer, has led to the greatest progress in cancer medicine that we’ve yet seen, according to City of Hope’s Stephen Gruber, M.D., Ph.D., M.P.H., the Eva and Ming Hsieh Family Director’s Chair of the Center for Precision Medicine.

Changing the view of genomics

Historically, clinicians sought very specific, individual genetic alterations that would answer pointed questions about a patient’s disease. Today, physicians and researchers are taking a more comprehensive look at patients’ genomes.  “In the beginning, we shined a spotlight on specific areas of the genome — kind of a ‘genetic snapshot’ approach,” Gruber said. “We focused on areas of the genome that we knew or suspected had major relevance based on research. As time has passed and the practice has advanced, City of Hope has turned its attention to the entire genome, taking a more panoramic approach.”

Traditionally, genomics has been implemented in a way where decisions are made on an individual basis. “Providers sit down and assess what’s indicated for each patient, what tests should be ordered, what company should be used for testing and whether the patient needs testing of both the tumor and their inherited DNA,” Stacy Gray, M.D., deputy director of the Center for Precision Medicine, explained. This creates two issues. The first is considerable variation in care. Some providers are more likely to order testing than others and some providers are more likely to put patients on targeted therapies. “The second problem is that an approach driven by individual patients and providers misses about half the people who could benefit from precision medicine,” Gray said. “This leads to complex and variable processes, as well as, and very importantly, inequities in cancer care.”

To deliver the greatest benefit, precision oncology requires standardization of care. City of Hope created an enterprise-wide system that enables all patients to benefit from precision medicine by participating in the INSPIRE study, which is open to any person — regardless of whether they have cancer or not — across City of Hope locations. A person who elects to participate is offered the option to undergo germline genetic tests for 189 genes related to risk of cancer and other medically actionable, disease-causing variants.

Genetic tests for inherited susceptibility have been shown to save lives for patients and their family members, and City of Hope’s panel of cancer genes is the most comprehensive test for cancer susceptibility. Since July 2020, 15,000 patients have enrolled in the study, 20% of whom have discovered a mutation that, in most cases, they were previously unaware of. “We extend this offer to everyone, so precision medicine is no longer a patient-by-patient decision,” Gray said. “It’s a decision that’s made for everyone across the health system. “This approach drives standardization of practice and processes. It lets us focus on what really matters most, which is the best possible care for our patients.”

Treating patients’ individual needs

Genetic research has typically centered on people of European heritage, but the Center for Precision Medicine, like all of City of Hope, is dedicated to diversity, equity and inclusion. “It’s embedded in everything we do because we have to make sure the information we use to care for patients is specific to who they are ancestrally, individually, personally and socially,” Gruber said. “This is infused into how we deliver precision medicine.” With precision medicine, physicians can identify the right treatments for patients and treat and prevent illness in family members. “We identified a person whose cancer was clearly related to an inherited predisposition to cancer,” Gruber said. “Within a month, we’d identified six family members who also carried that same susceptibility gene. That gave us an extraordinary opportunity to intervene and reduce the risk of cancer in those family members.”

Pioneering a new approach to cancer care

An important component of City of Hope’s precision medicine program is the Precision Oncology Tumor Board, which allows a patient to receive coordinated, multidisciplinary care. This program leverages real-world data from patient records and registries to modify each patient’s treatment based on their unique needs. In addition to testing patients for the genes associated with cancer risk, the analysis reviews a range of risk factors recommended by the American College of Genetics, including cardiovascular disease, providing lifesaving information that supports patient care, reaching far beyond cancer.

City of Hope has one of the largest cancer genetic counseling teams in the United States and is focused on treating the whole family since these gene changes are heritable. “This helps providers make decisions in a collaborative way with patients and their families,” Gray said. “We can give patients insight into what we know about their disease and why they got their disease. It relieves some of the stress for patients and families and enables them to make the best possible decisions during a very difficult time.”

City of Hope’s precision medicine program has yielded positive results and is widely embraced by the community it serves. Thanks to an enterprise-wide approach to inviting patients to provide consent into the precision medicine research protocol, City of Hope can offer genetic testing and genomic profiling at scale. “I think the future is very bright,” Gruber said. “We continue to be on the edge of discovery and, working with an incredible team here at City of Hope, we’re making progress every single day.”