Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer. (1st June 2023)

• Record Type: Journal Article
• Authors: Prajapati, Dipakkumar R.; Molczyk, Caitlin; Purohit, Abhilasha; Saxena, Sugandha; Sturgeon, Reegan; Dave, Bhavana J.; Kumar, Sushil; Batra, Surinder K.; Singh, Rakesh K.
• Is Part Of: Cancer letters. Volume 563(2023)
• Publication Date: 2023-06-01
• Subjects: Pancreatic cancer -- CXCR2 antagonist -- Tumor growth -- Angiogenesis -- Neutrophils -- Metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2023.216185
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis. Highlights: Systemic administration of CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist inhibited proliferation, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Selectively targeting CXCR2/1 is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.