2021 & 2022 Grantee: Gregory L. Beatty, MD, PhD
Perelman School of Medicine at the University of Pennsylvania
Research Project: Multiplex Tissue-based Assays and Analytical Tools for Pancreatic Cancer
Award: 2021 Pancreatic Cancer Action Network Precision Medicine Targeted Grant Extension in memory of Skip Viragh
2017 Pancreatic Cancer Action Network Precision Medicine Targeted Grant in memory of Skip Viragh
Award Period: July 1, 2021 – June 30, 2022
Amount: $200,000 ($800,000 total since 2017)
Award Extension: 2022 Pancreatic Cancer Action Network Precision Medicine Targeted Grant Extension funded by Leslie Gaynor in memory of Phyllis Bolotin
Award Period: July 1, 2022 – June 30, 2023
Amount: $200,000 ($1,000,000 total since 2017)
Dr. Beatty is an Associate Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania and in the Division of Hematology/Oncology within the Abramson Cancer Center at the Hospital of the University of Pennsylvania. Dr. Beatty also directs the Clinical and Translational Research Program in the Abramson Cancer Center Pancreas Program. Dr. Beatty graduated from Bucknell University with a BS in chemical engineering and then earned his PhD in immunology, followed by an MD from the University of Pennsylvania Perelman School of Medicine. He went on to complete a residency in internal medicine and a fellowship in medical oncology at the Hospital of the University of Pennsylvania.
Dr. Beatty’s research interest is in understanding mechanisms of immune escape in pancreatic cancer and translating novel immunotherapeutic strategies to the clinic for the treatment of patients with pancreatic cancer. He was the recipient of a 2015 Career Development Award from PanCAN and serves on the organization’s Scientific & Medical Advisory Board.
The microenvironment that surrounds cancer is a key regulator of therapeutic efficacy. For example, cancer-associated fibrosis can impede drug delivery and limit the benefit achieved with chemotherapy. Similarly, inflammation associated with cancer can promote treatment resistance to radiation, chemotherapy and immunotherapy. These challenges are particularly prevalent in pancreatic cancer patients.
Strategic and rapid development of novel therapeutic interventions will be dependent on defining elements of the cancer microenvironment that can be used to predict treatment response and inform treatment resistance. However, validated and effective tools for comprehensively analyzing the microenvironment in pancreatic cancer are still lacking.
The priority of Dr. Beatty’s project is to develop novel analytical tools for imaging multiple tissue-based markers (biological clues) to characterize the tissue microenvironment in pancreatic cancer. Specifically, the team will build a complex system to analyze pancreatic cancer and microenvironment tissue and visualize distinct proteins. Dr. Beatty and his colleagues will use this tool to measure cell-to-cell interactions and cellular activation, as well as to identify potential therapeutic targets, or proteins that could be blocked to stop or slow the growth of the tumor.
To date, Dr. Beatty and his team have built all 10 planned panels that assess the presence of certain proteins and other molecules within the tumor microenvironment. With the additional one year of funding, generously provided to honor the legacy of Skip Viragh, the investigators will apply their panels to samples from PanCAN’s Precision PromiseSM adaptive clinical trial. They will apply the analysis to tumor biopsies collected at baseline (before treatment) and after two months of treatment for patients treated on control arms within Precision Promise – 15 patients treated with gemcitabine/nab-paclitaxel and 15 patients treated with modified FOLFIRINOX.
With access to patient characteristics including progression-free survival, overall survival, mutational status and laboratory values, the investigators will also conduct exploratory analyses to define correlates associated with the tumor microenvironment and with patient outcome. As a second aim for this continuation funding, Dr. Beatty plans to incorporate a “stain-image-strip” process into their established method. This will permit the analysis of additional protein markers to further understand immune elements within the biopsy sample. Dr. Beatty described this technique as, “significantly expanding on the amount of information that we can obtain from tumor biopsy specimens with the hope that we can begin to understand the key features that dictate the behavior of pancreatic cancer and its response to treatment.”
Project Overview: 2022 Extension
The microenvironment that surrounds pancreatic ductal adenocarcinoma is a key determinant of treatment efficacy. With support from PanCAN, Dr. Beatty and his team developed and validated effective tools for comprehensively analyzing this microenvironment using a fully automated platform incorporating a technique known as multiplex chromogenic immunohistochemistry (mIHC). This allows the analysis of multiple components of the complex microenvironment at the same time. The team applied this approach to several settings: (i) pancreatic cancer liver biopsy specimens, (ii) tissues from SWOG1505 neoadjuvant chemotherapy (a clinical trial comparing two chemotherapy regimens in patients before undergoing pancreatic cancer surgery), (iii) tissues to inform determinants of immune responses to pancreatic cancer and (iv) samples from PanCAN’s Know Your Tumor® precision medicine service.
Here, Dr. Beatty and colleagues propose to apply their mIHC approach to study matched tumor biopsy specimens obtained from patients treated on control arms (Gemcitabine/nab-paclitaxel and mFOLFIRINOX) in the PanCAN Precision PromiseSM adaptive clinical trial. They’ll compare the microenvironment profiles of patients’ tumors before they begin treatment and after two months of treatment. They expect that this information will help inform rational combination strategies to pair with standard of care chemotherapy and in doing so, support the design of new treatment arms for Precision Promise.
The investigators will also develop “next generation” panels for mIHC to incorporate information about the tumor microenvironment and the immune response to the tumor. Their goal is to significantly expand on the amount of information obtained from tumor biopsy specimens. They will test the new mIHC panels on a test dataset of 10 banked pancreatic cancer samples. After validation, the team proposes to apply these new panels to their analysis of Precision Promise samples described above.
It is expected that these tools will contribute to the goal of doubling survival for pancreatic cancer by providing measures for defining prognosis, guiding treatment selection and instructing the development of novel therapeutic combinations for patients with pancreatic cancer.