Charis Eng, MD, PhD, FACP
Chairwoman, Genomic Medicine Institute, Cleveland Clinic
American Cancer Society Clinical Research Professor
Sondra J. and Stephen R. Hardis Chair of Cancer Genomic Medicine
Professor and Vice Chair, Department of Genetics
Case Western Reserve University
Uncovering the complex biology behind inherited cancers to better predict risk and discover new therapeutic strategies for patients.
Genetics are a major contributor to heritable breast cancer, but not all patients with mutated genes will develop the disease. For those who do develop cancer, scientists remain unsure as to why, and this hampers the design of effective predictive tests, prevention strategies, and therapies. BRCA mutations are the most well-known inherited mutations for breast cancer, but there are many more. Dr. Eng studies the gene PTEN, which her group identified as a tumor suppressor—it prevents healthy cells from becoming cancerous. When PTEN it is altered its tumor-blocking functions can be lost. The importance of PTEN is underscored in the familial cancer disorder PTEN Hamartoma Syndrome (PHTS). These individuals inherit mutations in PTEN and have an 85 percent risk of developing breast cancer and other cancers. Dr. Eng’s work explores what additional factors are required to tip the scales and initiate cancer in individuals with PHTS, which could also inform our understanding of how cancer forms in other heritable breast cancers.
Several biological factors could induce cancer in individuals with PTEN mutations, including additional inherited genetic alterations; spontaneous mutations that develop during a patient’s lifetime; and systemic, non-genetic, changes in the body (e.g., changes in metabolism or immunity). To further characterize the genetic makeup of PHTS cancers, and identify mutations that may contribute to cancer development, Dr. Eng’s team analyzed the DNA of 600 PHTS patients and their family members. Ultimately, they did find several genetic alterations that are associated with cancer in PHTS, which require further study. In addition, the team assessed breast tissues from PHTS patients to show that their cancers are genetically and molecularly different from non-PHTS breast cancers. The team also continued their study of the role of metabolism—tumors have their own unique processes for sugar, oxygen, and other nutrients—and found cancer-specific metabolites that could serve as biomarkers of cancer risk in PHTS.
To characterize the potential genetic and metabolic factors that can contribute to breast cancer risk in PHTS patients, the team will further their studies by assessing each PHTS patient’s unique genetic makeup and exploring if changes in metabolites are affected by a patient’s genetics. They will also assess PHTS’ patients breast cancer genomes to determine their cancers are distinct from those lacking an inherited PTEN mutation. This may result in new therapeutic and preventative drug targets for these patients. Overall, the proposed work is important for transforming our understanding of breast cancer development and prevention on an individual level.
Charis Eng, MD, PhD is the founding Chair of the Genomic Medicine Institute at the Cleveland Clinic, founding Director of the institute’s clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine. She was honored with the Hardis Endowed Chair in Cancer Genomic Medicine in 2008 and the American Cancer Society Clinical Research Professorship in 2009. In 2011, she was elected to the Institute of Medicine of the US National Academies of Sciences for her achievements and leadership in genetics- and genomics-based research and personalized healthcare. Her research has been acknowledged as the paradigm for performing cancer genetics research which can be brought to clinical practice. At the clinical interface, she is acknowledged as one of the rare "go to" people on what is and how to implement genetic- and genomics-enabled personalized healthcare.
The von Mandl Family Foundation Award
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