2. Academic Validation
  3. Targeting DDR2 for Treating Pancreatic Cancer

Targeting DDR2 for Treating Pancreatic Cancer

  • Mol Cancer Ther. 2025 Jun 26. doi: 10.1158/1535-7163.MCT-24-1226.
Chris Tp Do 1,  Prabhakar Pitta Venkata 2,  Jack Y Prochnau 3,  Deepika Singh 1,  Santosh Timilsina 4,  Panneerdoss Subbarayalu 5,  Daisy Medina 1,  Shahad Abdulsahib 1,  Saif Nirzhor 4,  Sajid Khan 1,  Guiming Li 1,  Srikanth R Polusani 6,  Daohong Zhou 2,  Pei Wang 1,  Yidong Chen 3,  Ratna K Vadlamudi 1,  Matthew J Hart 7,  Radhika Amaradhi 8,  Stanton F McHardy 9,  Manjeet K Rao 1
Affiliations

Affiliations

  • 1 The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • 2 The University of Texas Health Science Center at San Antonio, United States.
  • 3 The University of Texas Health Science Center at San Antonio, San Antonio, United States.
  • 4 The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States.
  • 5 Greehey Children's Cancer Research Institute, San Antonio, Texas, United States.
  • 6 University of Texas Health San Antonio, San Antonio, Texas, United States.
  • 7 University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
  • 8 The University of Texas at San Antonio, San Antonio, TX, United States.
  • 9 The University of Texas at San Antonio, San Antonio, Texas, United States.
PMID: 40568905 DOI: 10.1158/1535-7163.MCT-24-1226
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.

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