胰腺癌（PC）预后不良，当前治疗策略对晚期疾病无效。我们和其他人已经显示了 CXCR2 及其配体在 PC 发展和进展过程中的异常表达。我们本研究的目的是评估利用小分子拮抗剂 SCH-479833 靶向 CXCR2/1 的治疗效用，在不同的 PC 预临床小鼠模型（同基因或异基因）中。我们的结果显示，CXCR2/1 拮抗剂在 PC 中具有抗肿瘤和抗转移的效果。CXCR2/1 拮抗剂治疗抑制了肿瘤细胞增殖、迁移、血管生成和中性粒细胞的招募，同时增加了凋亡。拮抗剂治疗增强了纤维化、肿瘤坏死和骨髓外造血。这些发现表明，选择性地利用小分子抑制剂靶向 CXCR2/1 是一种有前途的治疗方法，可以抑制 PC 的生长、血管生成和转移。Copyright © 2023. Published by Elsevier B.V.

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.Copyright © 2023. Published by Elsevier B.V.