These grants represent a joint effort to stimulate novel research aimed at understanding the influence of the biology of the host (i.e., patient) on the genesis, development, treatment, and survivorship of cancer. Harnessing the powerful approach of examining cancer not as an isolated phenomenon but as a systemic disease, the funded projects are expected to yield important advancements in our understanding of cancer development, progression, and treatment.

2020 grantees

Research
Dr. Beatty’s group has previously found that hepatocytes, the chief functional cells of the liver, are instructed by cancer to support liver metastasis and has identified several molecular determinants that initiate this biology. However, it remains unclear how to therapeutically intervene on the liver as a strategy to enhance the immune response to cancer and to prevent metastasis. His goal is to define determinants of the liver response to human cancer and to interrogate mechanisms by which the liver coordinates immune dysfunction.

Biography
Dr. Beatty trained at the University of Pennsylvania (PhD in immunology, 2000; MD, 2004; residency 2004-2006; medical oncology fellow, 2006-2010). In 2012, he joined the faculty and now leads a discovery laboratory that uses mouse models, human tissues, and clinical trials to study mechanisms of resistance to immunotherapy with the priority to develop new treatment strategies. He is an associate professor of medicine in the Division of Hematology/Oncology and Director of Clinical and Translational Research for the Pancreatic Cancer Research Center.

Acknowledgment of Support
I am so thrilled to receive this grant award, which allows my research team and me to conduct studies on the connection between the liver, cancer, and immunity. Support from the AACR and The Mark Foundation will allow us to be innovative and to follow our vision of broadening the efficacy of immunotherapy.

Research
Obesity dramatically increases the risk of death from endometrial cancer, more so than any other cancer type. There are a variety of systemic changes that occur in the obese state that favor tumor initiation and progression. One of these factors, hyperinsulinemia, activates tumor phosphatidylinositol 3-kinase (PI3K) activity, which has been directly implicated in the pathogenesis of endometrial cancer. Therefore, dietary and pharmacologic strategies that lower insulin levels or block PI3K function may be effective anti-cancer agents in this setting. In this proposal, Dr. Goncalves will use mouse models and human clinical trials to test if a very low carbohydrate diet will reduce tumor insulin signaling, increase markers of cell death, and enhance the efficacy of PI3K inhibitors in endometrial cancer.

Biography
Dr. Goncalves obtained his MD/PhD degrees from the University of Pennsylvania and completed his postgraduate medical training at the joint program among Weill Cornell Medicine, New York Presbyterian Hospital, and Memorial Sloan Kettering Cancer Center. He is an endocrinologist and basic scientist at Weill Cornell Medicine in New York. His research focuses on the interactions between cancer and the hormones that regulate systemic metabolism. In his specialized clinical practice, he regularly treats patients with cancer experiencing hyperglycemia, weight loss, and other complications that may arise from their disease or care.

Acknowledgment of Support
I am honored to receive the 2020 AACR-The Mark Foundation for Cancer Research Science of the Patient Grant. Host factors are often overlooked in clinical trials and basic research. This unique grant provides critical support for us to highlight the role of diet and insulin in endometrial cancer progression.

Research
Weight loss, muscle wasting, adipose tissue reprogramming, and anorexia comprise a debilitating condition known as cachexia that is found in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Dr. Marks’s group has demonstrated that signaling between the tumor and the central nervous system (CNS) is critical for metabolic, behavioral, and neurocognitive complications during tumor growth. They have developed new models and compelling preliminary data demonstrating that preautonomic and neuroendocrine neurons located in the hypothalamus are activated early in the course of PDAC development and provide a robust catabolic output to peripheral tissues. These same pathways demonstrate remarkable phenotypic plasticity during the evolution of cachexia. These pathways provide novel therapeutic options for cachexia and include drugs that are already in clinical practice or advanced clinical trials.

Biography
Dr. Marks received medical and graduate training at the University of Washington, then completed his pediatric residency at the University of Utah and a fellowship in pediatric endocrinology at OHSU. He is currently Senior Associate Dean for Research at OHSU. He is also Professor and Ray Hickey Chair for Pediatric Research and Director of the Papé Family Pediatric Research Institute. His current investigations are focused on the neuroendocrine control of body weight. He has a particular interest in the brain mechanisms of disease-associated cachexia, with emphasis on cachexia in cancer patients and children with chronic disease.

Acknowledgment of Support
I am grateful to the AACR and The Mark Foundation for Cancer Research for the generous support offered by this award. We believe that the work supported by this grant will improve the lives of patients with cancer and point the way to new treatments for cachexia in cancer patients.

Research 
Population-based studies have identified disparities between racial groups in Head and neck squamous cell carcinoma (HNSCC) HNSCC treatment and survival, especially for patients with African ancestry. This disparity exists even after controlling for social determinants of health and access to care. This project aims to characterize the molecular features of HNSCC tumors specifically in patients with African ancestry, as defined computationally (rather than by self-reporting). In addition to genomic alterations, the project will also identify transcriptomic changes associated with HNSCC. Pathway analysis and integration of omics data can uncover tumor vulnerabilities in Black patients for therapeutic targeting.

Biography
Dr. Momen-Heravi received her PhD in molecular biology/biotechnology from the University of Westminster, UK. She pursued residency training in periodontics at Columbia University and performed postdoctoral research in molecular biology at Harvard Medical School and the University of Massachusetts Medical School. She is currently an assistant professor at Herbert Irving Comprehensive Cancer Center and the College of Dental Medicine at Columbia University. Her lab combines computational biology and advanced biostatical methods with wet lab techniques to identify signaling mechanisms and tumor vulnerabilities in head and neck cancer and lung cancer. Her group also works on novel genome editing modalities based on CRISPR/CAS and exosomes as precision medicine tools to treat cancer.

Acknowledgment of Support
It is an honor to receive the AACR-The Mark Foundation for Cancer Research Science of the Patient Grant. The grant supports the important mission of reducing health disparities in head and neck cancer. Our research will transform the lives of many minority patients by understanding their specific risk factors and developing new personalized treatment.

Research
The majority of cancer patients exhibit hepatitis following immune checkpoint blocker treatment. The molecular mechanism of immunotherapy-associated hepatic impairment and its effects on a patient’s metabolic microenvironment remain elusive. This research project aims to demonstrate the signaling events triggered by immune checkpoint blockers in hepatocytes and altered metabolic microenvironment-dependent acquired immune resistance, dissecting the interplay between the liver and the tumor microenvironment post-immunotherapy.

Biography
Dr. Yang joined the Department of Molecular and Cellular Oncology at the MD Anderson Cancer Center in 2013. He is a Cancer Prevention and Research Institute of Texas Scholar and an awardee of the Wilson S. Stone Memorial Award, Andrew Sabin Family Foundation Fellow Award, AACR-Bayer Innovation and Discovery Grant, AACR NextGen Stars Award, President’s Recognition of Faculty Excellence Awards, and Faculty Scholar Award. He is trying to find better treatments for acquired resistance to immunotherapy by thinking about the metabolic microenvironment in a new way.

Acknowledgment of Support
We are immensely thankful for the support provided by the AACR and The Mark Foundation. Our studies are aimed at improving clinical outcomes for a wide range of patients undergoing immunotherapeutic cancer treatments, and the discoveries made with the support of this grant will be critical to future considerations for immunotherapy.