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DEMYSTIFYING PANCREATIC CANCER THERAPIES

Increasing evidence finds that a pancreatic tumor’s microenvironment helps malignant cells survive chemotherapy and immunotherapy; and that, ironically, treatment-spurred changes to the microenvironment promote development of drug resistance. This project aims to discover exactly how that process occurs—creating knowledge that would underpin new, highly effective pancreatic cancer treatment strategies.

Increasing evidence finds that a pancreatic tumor’s microenvironment helps malignant cells survive chemotherapy and immunotherapy; and that, ironically, treatment-spurred changes to the microenvironment promote development of drug resistance. This project aims to discover exactly how that process occurs—creating knowledge that would underpin new, highly effective pancreatic cancer treatment strategies.

PROJECT HIGHLIGHTS

  • The project’s central hypothesis is that—to overcome the profoundly immunosuppressive microenvironment at work in pancreatic cancer tumors—it is necessary to develop therapeutic strategies targeting both the malignant cancer cells and the tissues that form their supportive environment.
  • It will test three therapeutic regimens delivered in the neoadjuvant setting—that is, drug combinations administered before a tumor is surgically removed—using a clinical trial design the research team previously demonstrated to be safe for use shortly before patients’ tumor-removal surgery.
  • The team will use the therapies in varied combinations designed to attack different aspects of pancreatic cancer survival.
  • Beyond carefully gauging the treatments’ clinical effectiveness, the researchers will expeditiously complete a multifaceted analysis of the surgically removed tumor and its microenvironment.
  • This analysis will use an array of cutting-edge methods to help identify the mechanisms by which the cancer cells develop resistance to treatment, and ensure that future trials routinely use such advanced technologies.

MEET THE TEAM

The Demystifying Pancreatic Cancer Therapies Project utilizes capacities provided by five leading clinical and research centers. This collaboration draws on cutting-edge expertise and technologies in areas ranging from deep genomic sequencing and liquid biopsy analysis to three-dimensional reconstruction and spatial transcriptomics. It also creates synergies among experts in areas ranging from cancer genomics and evolution to translational tumor immunology to computation biology.
We invite you to learn about the institutions and individual investigators driving this important research and development project.

AllDana-Farber Cancer InstituteMemorial Sloan Kettering Cancer CenterMIT’s Koch Institute for Integrative Cancer ResearchThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe University of Texas MD Anderson Cancer Center

MEET THE TEAM

The Demystifying Pancreatic Cancer Therapies Project utilizes capacities provided by five leading clinical and research centers. This collaboration draws on cutting-edge expertise and technologies in areas ranging from deep genomic sequencing and liquid biopsy analysis to three-dimensional reconstruction and spatial transcriptomics. It also creates synergies among experts in areas ranging from cancer genomics and evolution to translational tumor immunology to computation biology.
We invite you to learn about the institutions and individual investigators driving this important research and development project.

View Team
AllDana-Farber Cancer InstituteMemorial Sloan Kettering Cancer CenterMIT’s Koch Institute for Integrative Cancer ResearchThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe University of Texas MD Anderson Cancer Center

PROJECT SUMMARY

One reason pancreatic cancer has proven so deadly is that its cells often become both resistant to chemotherapy and very effective at evading the body’s natural immune response. Research strongly suggests that the tumor’s microenvironment contributes substantially the ability to develop drug resistance and to evade immune response.

Therefore, this project will explore therapeutic strategies that can target both the malignant cancer cells themselves and the multiple components in the stromal tissue—the non-cancer and non-immune cells that help hold the tumor together—that forms its microenvironment. To that end, the research team will pursue a “bench-to-bedside-to-bench” cycle of continuous knowledge-gathering: testing specific drugs combinations and, in parallel, using an array of cutting-edge techniques to analyze how tumor cells and the microenvironment adapt to the treatments.

The project’s knowledge-gathering cycles will focus on a series of three neoadjuvant therapy clinical trials. The trials will use a research design that the project team previously demonstrated to be safe and feasible in testing a new treatment strategy in the two weeks prior to surgical removal of a pancreatic tumor. The first of these clinical trials will evaluate a drug combination (an IL-8-CXCR1/2 inhibitor and an anti-PD-1 antibody) that had been the focus of a smaller study funded by the Lustgarten Foundation and will now be converted into a larger, multi-institutional trial. The project’s subsequent clinical trials will be selected in consultation with clinical experts in pancreatic surgery and medical oncology and with thought leaders in translational therapeutic development.

The project’s multifaceted analytical activities will be accomplished through the creation of a complex, collaborative study platform that incorporates expertise and state-of-the-art technologies from five leading institutions. In addition to tracking clinical impact, this powerful platform will study—at three-dimensional and single-cell levels—how the tumor microenvironment changes during the therapy and how the cancer cells adapt to the treatments.

The research team’s studies will include systematic analysis of post-treatment tumor specimens and of liquid biopsies using diverse genomic technologies. Such investigations will, for example, enable investigators to longitudinally monitor tumor genomic evolution through tissue. The scientists will also be able to use data on cells’ transcriptional signatures to quantify different tumor cell states and, subsequently, identify resilient tumor cells and the microenvironmental characteristics that empower them.

Thus, the study platform will enable the research team to accomplish two goals in parallel: comparing the effectiveness of three different treatment combinations, while rapidly advancing the scientific knowledge—such as discovery of cells’ response signatures and of possible resistance mechanisms—necessary to drive a breakthrough in pancreatic cancer therapies.

MAKE A DIFFERENCE

Break Through Cancer was created in February 2021 with an extraordinary matching gift of $250,000,000. Every gift to the Foundation supports groundbreaking cancer research and helps us to meet our matching commitment.

For questions about giving please email Lisa Schwarz, Chief Philanthropy Officer at LMS@BreakThroughCancer.org

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