2021 Grantee: Charline Ogier, PhD
Fox Chase Cancer Center
Research Project: Preclinical Evaluation of Netrin-1 Antibody for Treatment of Pancreatic Cancer
Award: 2021 Pancreatic Cancer Action Network Fellowship funded by The Francois Wallace Monahan Fund in loving memory of Michael Insel
Award Period: July 1, 2021 – June 30, 2023
Dr. Charline Ogier joined the Montpellier Cancer Institute (France) for her PhD under the supervision of Dr. Christel Larbouret. She dedicated her time exploring a new therapeutic perspective for pancreatic cancer: targeting proteins expressed by the tumor and its microenvironment that attach to human epidermal growth factor receptors (HER). During these four years, she reported an antitumor activity of blocking a protein called neuregulin (NRG)’s availability in the tumor area, with an innovative anti-NRG antibody, together with its anti-migratory effect and drastic decrease of signaling pathway related to HER receptors.
She decided to pursue her career in research against pancreatic cancer, especially in tumor-microenvironment interactions by integrating the laboratories of Drs. Edna Cukierman and Igor Astsaturov in 2018 at Fox Chase Cancer Center (Philadelphia, USA). From there, she is working in collaboration with Drs. Patrick Mehlen and Darren Carpizo, recipients of the 2018 PanCAN Translational Research Grant, on her project titled “Preclinical Evaluation of Netrin-1 Antibody for Treatment of Pancreatic Cancer.” The ultimate goal is to provide the pre-clinical data needed to support the design of a clinical trial. She believes this treatment has remarkable promise to increase the survival of pancreatic cancer. This project is a steppingstone for Dr. Ogier to establish herself as a pancreatic cancer scientist with an innovative and self-sustained research program.
Previous data have shown that netrin-1 (NTN1) is expressed in pancreatic cancer cells and that the protein plays a role in the cells’ survival and ability to metastasize, or spread. Dr. Ogier’s collaborative project is exploring the mechanisms of cellular communications via NTN1 as a new therapeutic target in pancreatic cancer. She is testing anti-pancreatic cancer activity of a new therapeutic monoclonal antibody called NTN1-mAb developed by Dr. Patrick Mehlen at the Research Cancer Center of Lyon, France, in collaboration with Dr. Carpizo’s lab. The goal of Dr. Ogier’s project is to determine the mechanism of activity and to define biomarkers to select patients most likely to benefit from this treatment using pre-clinical pancreatic cancer models.
First, Dr. Ogier will explore the effectiveness of NTN1-mAb in the treatment of mice genetically programmed to develop pancreatic cancer through the same genetic alterations common in human disease. She will determine whether blocking the activity of NTN1 with the NTN1-mAb will slow the tumor growth, prevent metastatic spread and increase the survival of the mice.
Dr. Ogier and her team hypothesize that blocking NTN1 will prevent the transition from epithelial cells into mesenchymal cells, a necessary step in the metastatic development of pancreatic cancer. Her second aim will focus on validating that the NTN1-mAb leads to an enhancement in the epithelial cell population within the tumor and also impacts the tumor’s microenvironment, utilizing the mice genetically programmed to develop pancreatic cancer. Dr. Ogier will then analyze whether NTN1-mAb sensitizes pancreatic tumors in the mice to treatment with chemotherapy and immunotherapy approaches.
Overall, this project will provide the pre-clinical data needed to support the design of a clinical trial of anti-Netrin-1 antibody in pancreatic cancer patients.