Abstract B030: Targeting DDR2 for Treating Pancreatic Cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with limited effective treatments, partly due to its complex tumor microenvironment. Herein, we report Discoidin Domain Receptor 2 (DDR2), a receptor tyrosine kinase, as a critical protein that promotes PDAC growth and survival. Our results reveal that DDR2 is highly expressed, and its expression correlates with the worst survival outcome of PDAC patients. Using an unbiased high throughput screen of small molecule inhibitor libraries, we identified CIDD-8633, a novel inhibitor targeting DDR2. Our study suggests that CIDD-8633 interacts with DDR2 and inhibits DDR2-associated signaling. Importantly, in vivo studies demonstrate that CIDD-8633 effectively blocks PDAC tumor growth in preclinical mouse models. Additionally, combining CIDD-8633 with gemcitabine enhanced its efficacy synergistically. Mechanistically, CIDD-8633 treatment induces pro-apoptotic genes in PDAC cells. These findings position DDR2 as a promising therapeutic target and CIDD-8633 as a potential DDR2 inhibitor, offering new avenues for treatment of PDAC. Citation Format: Chris TP. Do, Stanton McHardy, Manjeet Rao. Targeting DDR2 for Treating Pancreatic Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B030.