2023 Grantee: Ivana Peran, PhD
Georgetown University’s Lombardi Comprehensive Cancer Center
Research Project: Role of Stromal Cadherin 11 in Chemotherapy Response in Pancreatic Cancer
Award: 2023 Pancreatic Cancer Action Network Career Development Award
Award Period: July 1, 2023 – June 30, 2025
Dr. Ivana Peran is an Assistant Professor at Georgetown University’s Lombardi Comprehensive Cancer Center. After completing her master’s degree in Molecular Biology from the University of Zagreb, Dr. Peran earned her doctoral degree in Tumor Biology at Georgetown University as a Fulbright Science and Technology Scholar. During her post-doctoral research on immunomodulation of pancreatic cancer, Dr. Peran was awarded a research grant by the Ruesch Center for the Cure of Gastrointestinal Cancers as well as an AACR-AstraZeneca Fellowship in Immuno-oncology Research. In addition, she received an invitation to the fourth annual Immuno-Oncology Young Investigators’ Forum.
Dr. Peran has over 13 years of experience in pancreatic cancer translational research. For the last decade, she has been studying an interplay of pancreatic cancer-activated fibroblasts and immune cells within the tumor microenvironment, which in turn has an impact on the tumor growth. Moreover, Dr. Peran has been working on identifying new therapeutic strategies that target an adhesion molecule, cadherin 11 expressed on cancer-associated fibroblasts, in combination with the standard-of-care chemotherapy.
The dismal statistics on pancreatic cancer survival and lack of effective treatment options prompted Dr. Peran and her team to seek a new avenue for treating this devastating disease. Instead of solely targeting cancer cells, they focus on the pancreatic cancer microenvironment that contains various non-cancer cells, which may comprise up to 80-90% of tumor tissue. These abundant cells, called fibroblasts, feed tumor growth, and cancer cells induce the recruitment of more fibroblasts to the microenvironment. In their previous work, the investigators found that in pancreatic cancer, these non-cancerous cells make high levels of a protein called cadherin 11, which is not found in the normal pancreas. It has been previously shown that cadherin 11 is important in other diseases associated with chronic inflammation, which is the most significant risk factor for pancreatic cancer development.
Dr. Peran and her team hypothesize that fibroblasts prevent proper functioning of the immune system against cancer cells, keeping it in a suppressed state when cadherin 11 is abundant. In their preliminary studies, they discovered that loss or inhibition of cadherin 11 significantly extends survival of mice with pancreatic cancer by promoting an anti-tumor immunity that fights against cancer more efficiently. Moreover, this new cancer environment, infiltrated with anti-tumor immune cells, was more susceptible to chemotherapy.
For her PanCAN Career Development Award, Dr. Peran’s project aims to identify an optimal therapeutic sequence of cadherin 11 inhibition combined with standard-of-care chemotherapy in mice. The Peran lab will also assess tumor growth and immune cell infiltration into the tumor microenvironment. Using a genetically engineered mouse model of pancreatic cancer, they will compare the results of blocking cadherin 11 with a drug vs. loss of the protein through genetic manipulation. Finally, the research team will utilize a novel technology known as spatial proteomics to study the interactions of immunosuppressive cells (tumor-promoting cells) and anti-tumor immune cells with each other and with cancer cells, fibroblasts and blood vessels.
The goal of this project is to understand how inhibition of cadherin 11 might strengthen the immune system’s response to the tumor and make standard-of-care chemotherapy more effective. These findings could be rapidly translated into the clinic to benefit pancreatic cancer patients and possibly patients with other cadherin 11-positive diseases.