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AACR-Johnson & Johnson Lung Cancer Innovation Science Grants

Because of the late onset of clinical symptoms and inadequate screening programs, nearly two-thirds of all lung cancers are diagnosed at an advanced stage and, as a result, five-year survival rates are still below 18 percent. Simple yet accurate diagnostic tools that can improve the detection of early lung cancers are urgently needed. These grants represent a joint effort to address the need for promoting and supporting collaborative cancer research to bolster our understanding of how lung cancer can be successfully intercepted. Projects are implemented by multi-institutional teams composed of principal investigators from at least two, but no more than three, different institutions and include a clinical component with an endpoint relevant to improving the detection or treatment of lung cancer.

2018 Grantees

Microenvironment-mediated clonal evolution and risk of lung adenocarcinoma

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Lead Principal Investigator: James V. DeGregori, PhD 
Professor
University of Colorado Denver, AMC and DC
Aurora, Colorado

Bruno_90x110.jpgCo-Principal Investigator: Tullia C. Bruno, PhD
Research Assistant Professor
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania

Scientific Statement of Research
Prior discovery has revealed an important role for alterations in lung tissue microenvironment in pre-malignant progression and increased cancer risk. Despite this knowledge, our ability to assess these changes in the early stages of lung adenocarcinoma development is extremely limited. In this project, we will identify oncogenic clonal evolution and associated immune microenvironment changes that precede development of lung adenocarcinoma. We will characterize changes in clonal evolution, airway progenitor function, and the immune/inflammatory landscape in the peripheral lung field using brushings from individuals undergoing standard of care workup of CT-detected lung nodules. We postulate that changes in the lung microenvironment will promote selection and persistence of adaptive oncogenic events, indicating field cancerization even at sites remote from the malignant nodule. Monitoring clonal evolution and microenvironmental features should reveal parameters that indicate a landscape supportive of the premalignant evolution of pulmonary adenocarcinoma and may be useful in defining risk and developing preventive interventions.  

Biographies

Dr. DeGregori is a professor in the Department of Biochemistry and Molecular Genetics and deputy director of the University of Colorado Cancer Center. He holds the Courtenay and Lucy Patten Davis endowed chair in lung cancer research. He received a BA in microbiology from the University of Texas at Austin in 1987, a doctorate in biology from the Massachusetts Institute of Technology in Cambridge in 1993, and postdoctoral training at Duke University from 1993-1997. His lab seeks to understand how carcinogenic conditions promote cancer evolution and to discover pathway dependencies in cancers that can be exploited therapeutically.

Dr. Bruno is an assistant professor in the Department of Immunology at the University of Pittsburgh and a faculty member in the Tumor Microenvironment Center at the UPMC Hillman Cancer Center. She obtained her doctorate in immunology from Johns Hopkins in 2010 and completed her postdoctoral fellowship at the University of Colorado in 2015, both with a focus in tumor immunology. While Dr. Bruno’s PhD training focused on inhibitory receptors on intratumoral T cells, she became interested in tumor infiltrating B cells during her postdoctoral fellowship and has built her independent research program around understanding their function in multiple human cancers, in particular, lung and head and neck cancers. Dr. Bruno’s overall research objective is to develop a TIL-B-specific immunotherapy in the next five to 10 years.

Acknowledgement of Support
We want to thank the AACR and Johnson & Johnson for their generous support for our team project. This Lung Cancer Innovation Science Grant should facilitate a better understanding of how monitoring changes in peripheral lung tissue can help distinguish individuals at greatest risk of lung cancer and should enable the development of preventative interventions. 

Candidate immune markers for early detection of lung cancer

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Lead Principal Investigator: Dominique Michaud, ScD 
Professor
Tufts University School of Medicine
Boston, Massachusetts

Kelsey_Karl_90x110.jpgCo-Principal Investigator: Karl T. Kelsey, MD 
Professor
Brown University
Providence, Rhode Island

Platz_Elizabeth_90x110.jpgCo-Principal Investigator: Elizabeth A. Platz, ScD, MPH
Professor
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland

Scientific Statement of Research
The overall goal of this project is to examine relationships between antibodies to periodontal disease bacteria, peripheral blood immune profiles, and lung cancer risk. The aims of this project will be conducted using existing banked pre-diagnostic bloods obtained at two different time points in the same individuals (CLUE I/II cohorts), in some cases up to 25 years prior to lung cancer diagnosis. Immune cell types will be measured using DNA methylation (cell specific markers) obtained from archived white blood cells. Findings from this project will provide insight into the latency period between periodontal disease development and lung cancer incidence, and inform on the nature of the etiological role of the immune response in lung cancer. In addition, this project could have direct translational potential as it may identify mechanistically-based biomarkers that could serve to improve risk stratification for early detection of lung cancer.

Biographies
Dr. Michaud is a professor in the Department of Public Health and Community Medicine at Tufts University Medical School. She obtained her doctoral degree in epidemiology from the Harvard School of Public Health. Her research expertise is in nutritional, molecular, and cancer epidemiology. Her current research focuses on oral health and microbiome as they relate to cancer risk. She has received numerous NIH grants and is currently funded to examine DNA methylation patterns and pancreatic cancer. Dr. Michaud has co-authored over 150 peer-reviewed publications, and is engaged in teaching graduate students at the Tufts Medical School.

Dr. Kelsey’s research has centered upon the development and application of biomarkers useful for population-based studies. His group was among the first to use genomic approaches to ask questions about how the biological effects of environmental exposures are modified by normal genetic variation. The laboratory has also been among the first to extend genetic investigations into studies of epigenetics and modifications of the expression of important genetic changes. His current research interest is focused on deepening our understanding of the potential environmental contributors to alterations of the immune system.

Dr. Platz is professor, Martin D. Abeloff, MD Scholar in Cancer Prevention, and deputy chair of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health, where she directs the NCI-funded (T32) training program in Cancer Epidemiology, Prevention, and Control. She also co-leads the Cancer Prevention and Control Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and holds joint appointments in the Department of Oncology, and the Department of Urology and the James Buchanan Brady Urological Institute at the Johns Hopkins University School of Medicine. She received her doctorate in epidemiology from and was a postdoctoral fellow at the Harvard School of Public Health. A major focus of her work is the use of molecular and genetic epidemiology approaches to understand the mechanisms underlying prostate incidence and progression. She conducts her work with an eye toward translation of findings into prevention and treatment strategies.

Acknowledgement of Support
The AACR-Johnson & Johnson Lung Cancer Innovation Science Grant will provide our multidisciplinary team with the funding necessary to address a number of novel and compelling hypotheses that will provide insight into immune alterations that occur many years prior to lung cancer diagnosis, potentially allowing for identification of new early detection biomarkers.

Immunogenomic and microbiota evolution from premalignancy to lung cancer

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Lead Principal Investigator: Jianjun Jay Zhang, MD, PhD 
Assistant Professor
University of Texas MD Anderson Cancer Center
Houston, Texas

Heymach_John_90x110.jpgCo-Principal Investigator: John V. Heymach, MD, PhD
Professor
University of Texas MD Anderson Cancer Center
Houston, Texas

Pass_Harvey_90x110.jpgCo-Principal Investigator: Harvey I. Pass, MD
Professor
NYU Langone Medical Center
New York, New York

Scientific Statement of Research
Our understanding of early lung carcinogenesis and mechanisms of postsurgical recurrence of lung cancer is rudimentary. There is growing evidence from our group and others that the escape from immune surveillance plays a critical role in the progression from premalignancy to invasive lung cancer, as well as in postsurgical recurrence and that both the molecular landscape and microbiota can impact neoplastic progression and postsurgical recurrence. In this proposal, we aim to comprehensively characterize the molecular, immune, and microbiome landscape of lung premalignancy as it evolves to early stage lung cancer; and to assess the factors within this landscape that determine the postsurgical recurrence and response to immunotherapy. We envision that this project will generate pivotal data to significantly advance our understanding of lung cancer initiation, progression and postsurgical recurrence and to provide novel insights for precise diagnosis, effective prevention and treatment of lung cancers.

Biographies
Dr. Zhang received his MD from Tongji Medical University and PhD from Peking Union Medical College in China. He completed a research fellowship in Memorial Sloan Kettering Cancer Center before residency training at the Long Island Jewish Medical Center. He joined the Department of Thoracic/Head Medical Oncology at MD Anderson Cancer Center in 2015 . He is a physician-scientist with research interests that include elucidating the molecular and immune evolution of lung cancer, mechanisms and translational implications of tumor heterogeneity, and the impact of cancer molecular features on host antitumor immune surveillance.

Dr. Heymach is a physician-scientist and chair of the Department of Thoracic/Head and Neck Medical Oncology (THNMO) at MD Anderson Cancer Center. He currently holds the David Bruton, Jr. chair in cancer research. He attended Harvard College, where he graduated magna cum laude with a BA in chemistry in 1989 and received his MD and PhD degrees from Stanford in 1998. He completed his internship and residency in internal medicine at Brigham and Women’s Hospital and his medical oncology fellowship at Dana-Farber/Partners HealthCare. He joined the faculty at MD Anderson in 2005 and became chair of the THNMO department in 2013. He has been a productive clinical and laboratory investigator, with more than 180 peer-reviewed publications, and has led a well-funded laboratory with funding that includes three NCI R01 awards, co-leadership of Lung and HN SPORE projects, two AACR-SU2C “Dream Teams,” a V Foundation Research Award, a CPRIT Multi-Investigator Award, and numerous other foundation awards. Advances from his laboratory include the discovery of new therapeutic targets for small cell lung cancer; identification of new biomarkers and mechanisms of resistance to VEGF and EGFR inhibitors; and the recent recognition that KRAS-mutant lung cancers can be divided into biologically distinct subgroups based on genomic profiles, and that these subgroups predict response to immunotherapy and other treatments.

Dr. Pass is a surgeon scientist whose translational work focuses on the early detection, surgical management, and adjuvant therapy of thoracic malignancies. He graduated from Duke University Medical School and finished cardiothoracic surgery training at the Medical University of South Carolina. He has served as became chief of thoracic oncology at the NCI and the Barbara Ann Karmanos Cancer Center. Since 2006, Dr. Pass has served as the division chief of general thoracic surgery, vice chair for research for the Department of Cardiothoracic Surgery, and  Stephen E. Banner professor of thoracic oncology for the NYU Langone Medical Center.
 
Acknowledgement of Support
We sincerely appreciate the AACR and Johnson & Johnson for the 2018 Lung Cancer Innovation Science Grant to support our project, which we envision will provide novel insights for precise diagnosis, effective prevention, and treatment of lung cancers.


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