Posted November 30, 2021

Dr. Kirsten Bryant and Dr. Channing Der, University of North Carolina, Chapel Hill
Dr. Meredith Stone and Dr. Gregory Beatty, University of Pennsylvania

The Pancreatic Cancer Research Program (PCARP) was initiated in fiscal year 2020 (FY20) to promote rigorous, innovative, high-impact research leading to new pancreatic cancer diagnostic and therapeutic tools through collaboration. The PCARP’s Strategic Direction includes four key elements that drive the program and are instrumental to fulfilling its mission. One of the four elements includes recruiting and training young investigators that are dedicated to pancreatic cancer research. In the first year of the program, two early-career investigators, with their partnering PI, were funded through the Idea Development Award (IDA), which supports innovative, high-risk/high-reward research ideas that will accelerate progress in improving outcomes for those with pancreatic cancer. The Early-Career Investigator option within the IDA creates an opportunity to partner experienced investigators with early-career investigators wishing to pursue a career in pancreatic cancer research through mentorship and collaboration. For FY20, Dr. Kirsten Bryant and Dr. Meredith Stone, along with their partnering PIs, were funded through the Early-Career Investigator Option.

Dr. Kirsten Bryant was awarded an FY20 IDA working under the mentorship of Dr. Channing Der at of the University of North Carolina, Chapel Hill. Drs. Bryant and Der’s proposed work will primarily address the PCARP Focus Area, “New drug development targeted toward cancer sensitivity and resistance mechanisms including immune mechanisms of resistance,” by identifying metabolism-related genes that regulate ERK and autophagy activity. The Principal Investigator’s (PI’s) studies are based on the combination use of ERK and autophagy inhibitors that are currently in clinical trials and aim to identify second-generation combinations that will powerfully inhibit pancreatic ductal adenocarcinoma (PDAC). Using advanced screening techniques, the PI will identify the best candidate gene targets and then assess experimental combinations of inhibitors of these targets via using in vitro and in vivo models. Drs. Bryant and Der anticipate their genetic screens will identify multiple potential gene targets and combinations and, importantly, identify combinations that will overcome resistant disease.

Dr. Meredith Stone was awarded an FY20 IDA working under the mentorship of Dr. Gregory Beatty at the University of Pennsylvania. Drs. Stone and Beatty’s study will advance knowledge in the PCARP Focus Areas, “Development of pharmacological, immunological, or genetic interception approaches,” and “Understanding the events that promote pancreatic cancer metastasis.” Preclinical models have shown the importance of the tumor microenvironment (TME) in PDAC as a barrier to immunotherapy, and Drs. Stone and Beatty aim to define the liver as a therapeutic target capable of reversing resistance to immunotherapy and reducing the risk of metastasis. The PIs have observed that serum amyloid A proteins (SAA) are released in the liver by hepatocytes in response to IL-6, a cytokine found in the TME. This study is designed to define the mechanisms originating in the liver that regulate T cell immunosurveillance in PDAC and define the role of the liver as a determinant of immune resistance to immunotherapy. Drs. Stone and Beatty plan to develop therapeutics to intervene in liver-directed immune dysfunction in pancreatic cancer. They expect their findings to lead to the initiation of clinical studies focused on targeting the liver to improve treatment outcomes in PDAC patients.

These two awards have begun to lay the foundation for one of the key elements of the PCARP’s strategic goals by investing in early-career investigators that are devoted to finding new treatment avenues and diagnostic tools that are lacking in the pancreatic cancer community.

Links:

Public and Technical Abstracts:  Targeting KRAS-Dysregulated Metabolism for Novel Therapeutic Approaches

Public and Technical Abstracts:  Targeting Hepatocyte-Derived Factors to Improve the Efficacy of Immunotherapy in Pancreatic Cancer

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