Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.

I am an Assistant Professor of Medical Oncology who primarily treats patients with colon cancer and gastroesophageal cancers. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, particularly in the setting of metastasis. This work has led to a specific interest in tumor-mediated development of dendritic cell tolerance and suppressive myeloid populations. The ultimate goal of this research is to create biomarker-directed immunotherapies for advanced gastrointestinal cancers.

Dr. Beasley is an associate professor of surgery in the division of Surgical Oncology at Duke University with a secondary appointment as associate professor in the department of medicine.  After playing 3 years in the women’s NBA, she began medical school. She obtained her MD (2008) and Masters of Health Science in clinical research (2010) from Duke University School of Medicine.  She then completed general surgical residency at Duke University in 2015, during which time she was awarded a traineeship under a long-standing Surgical Oncology T32 grant. She then completed a fellowship in complex surgical oncology at the Ohio State University in 2017. She returned to Duke in 2017 as a faculty member. In 2019, she became co-director of the Duke Melanoma Program.

Dr. Beasley is a surgeon scientist with active involvement in clinical and translational research. Her main clinical and research interests include immunologic aspects of melanoma including oncolytic viral therapy.  She is principal investigator of over 10 therapeutic clinical trials in melanoma including novel intratumoral therapies. Her research focuses on the role of innate immunity in the anti-tumor response. She has authored over 100 publications centered on melanoma. She has received multiple internal and external funding including the Society of Surgical Oncology’s Young Investigator Award, NIH K08 mentored physician scientist award, and Melanoma Research Alliance Grant..  Most recently she was selected to Duke Medical School’s Alpha Omega Alpha and received the American Society for Clinical Investigation Young Physician-Scientist Award.

John Strickler, MD is a Professor of Medicine in the Division of Medical Oncology, where he is Co-Leader for the Precision Cancer Medicine and Investigational Therapeutics Program at the Duke Cancer Institute, Leader of the Molecular Tumor Board, and Associate Director of Clinical Research – GI Oncology. Dr. Strickler’s clinic specializes on the treatment of gastrointestinal malignancies, with a particular emphasis on gastroesophageal, pancreatic, and colorectal cancers. His research focuses on precision cancer medicine: identification of biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy. He has designed and executed clinical trials that test novel therapies and innovative therapeutic strategies. He was Principal Investigator on an investigator sponsored trial that led to the first FDA-approved therapy for HER2+ metastatic colorectal cancer. He has first-author publications in several high impact factor medical journals, including the New England Journal of Medicine, Clinical Cancer Research, Cancer Discovery, Journal of Clinical Oncology, and Lancet Oncology. Nationally, he has served as a member of the American Society of Clinical Oncology (ASCO) Treatment Guidelines Committee for Advanced Colon Cancer.

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
2. Studying the relationship between EMT pathways and immunotherapy resistance.
3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
5. Investigating mechanisms contributing to select immunotherapy-associated toxicities