April 26, 2022

Because Cancer is Not an Island: Progress in the AACR-The Mark Foundation for Cancer Research “Science of the Patient” SOP Grants

By the American Association for Cancer Research

“Tumors do not grow in a vacuum,” says Marcus DaSilva Goncalves, MD, PhD, Assistant Professor at Weill Cornell Medicine, and an endocrinologist who is investigating the effects of insulin on tumor growth. His team is using dietary interventions and anti-diabetic drugs to lower insulin in mice and patients to determine the effects on tumor growth and metabolism. Their long-term goal is to develop new diet-drug combination therapies for cancer. The team has already found that lowering insulin levels with a ketogenic diet in patients with uterine cancer alters tumor signaling and metabolism. Dr. Goncalves says, “This work would not have been possible without support from The AACR and The Mark Foundation for Cancer Research because dietary interventions are complex to perform and considered too risky for a traditional funding source.”

Dr. Goncalves is one of five recipients of the 2020 AACR-The Mark Foundation for Cancer Research “Science of the Patient” SOP Grant. This Grants Program is a joint effort to stimulate novel research on the interplay between patient physiology and the tumor. The five grantees are performing breakthrough research studying cancer not as an isolated phenomenon but as a systemic disease – that affects and is affected by the normal and pathological functions of the patient’s body. The funded projects are broad in scope and range from examining the relationship between cancer and host organs such as the liver and brain, to investigating the patient’s diet and ancestry.

Gregory L. Beatty, MD, PhD, Director of Clinical and Translational Research Program at the Pancreatic Cancer Research Center and Associate Professor at the University of Pennsylvania, is investigating the interplay between cancer and the liver. The liver plays an important role in “educating the immune system to be tolerant to normal proteins present in the body,” says Dr. Beatty. However, cancer can co-opt this process to evade the immune system. Dr. Beatty’s goal is to understand the mechanisms of liver-mediated immune evasion and to improve the efficacy of immunotherapy. The team has developed mouse models to recapitulate the liver-cancer interactions that occur in patients and have identified inflammatory signals released by the liver that help cancer immune evasion. He says, “Support from this grant mechanism has allowed us to be bold and creative in our studies. It has provided the opportunity to be nimble in choosing the direction of our studies to be most impactful.”

Characterizing the molecular landscape of head and neck tumors, with a focus on minority populations, is the research goal of Fatemeh Momen-Heravi, DDS, PhD, MPH, MS, Director of the Head and Neck Cancer Research Group, Herbert Irving Comprehensive Cancer Center, and Associate Professor at the Columbia University Medical Center. Head and neck cancers are devastating, more so for patients of African ancestry who have higher incidence rates and worse treatment outcomes. Precision medicine efforts have focused largely on White patients, which Dr. Momen-Heravi hopes to change. She says, “The AACR-The Mark Foundation for Cancer Research SOP grant was a transformative opportunity for us to pursue this project in an early stage as a high risk/high reward project.” Her group has identified novel and targetable molecular features of head and neck cancer in Black patients, which will aid in the development of personalized therapies and reduce cancer disparities.

Immunotherapies can dampen the liver’s ability to metabolize dietary protein resulting in the accumulation of phenylalanine. Liuqing Yang, PhD, Associate Professor at The University of Texas MD Anderson Cancer Center is investigating how this excess phenylalanine contributes to acquired resistance to immunotherapy (where the tumor progresses after initial response). Dr. Yang’s team has found that elevated phenylalanine modulates the tumor microenvironment by inhibiting tumor-associated neutrophils, and that the FDA-approved phenylketonuria drug sapropterin prevents immunosuppression. He says, “The generous support from the AACR-The Mark Foundation SOP grant has provided opportunities to collaborate with nationally and internationally recognized clinicians and researchers to further our mission of tackling the mechanisms of immunotherapy.”

“The ‘Science of the Patient’ mechanism is rather unique in cancer research in that it explicitly focuses on the impact of cancer on the body, rather than on cancer biology itself,” observes Daniel L. Marks MD, PhD, Senior Associate Dean of Research and Professor of Pediatric Endocrinology at Oregon Health & Science University (OHSU). He adds that this grant was “a perfect opportunity for a neuroscientist like myself to increase my visibility and collaboration with the cancer community.” Dr. Marks is exploring the role of the nervous system in cachexia and adverse neurocognitive symptoms experienced by cancer patients. Cachexia decreases the patient’s quality of life and limits the utility of cancer therapies. A key collaborator, Dr. Aaron J. Grossberg, Assistant Professor at OHSU, describes cancer as a constant stressor that activates the “fight-or-flight” response. Using a model of head and neck cancer, the team is researching the link between this response and cachexia and developing drugs that can treat cachexia in a wide range of tumors. The team has learned that cancers vary in their ability to cause cachexia and has developed a way to measure cachexia in patients using CT scans and machine learning tools.

The AACR-The Mark Foundation for Cancer Research SOP Grants program is expected to advance our understanding of cancer development, progression, and response to treatment, and catalyze the development of innovative therapies. The encouraging results already generated by this grant mechanism offer an optimistic outlook for consequential discoveries that will emerge from this paradigm-shifting approach to cancer research.

Reprinted by permission (c) AACR

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