局部晚期直肠癌（RC）患者的治疗基于新辅助放化疗，然后进行手术。为了减少治疗耐药的产生，有必要进一步改进以往的治疗方法。最近的体内实验研究表明，通过抑制糖酵解激活剂PFKFB3，通过肿瘤血管正常化（TVN）减少肿瘤缺氧，可以显着改善肿瘤对治疗的反应。我们在体外和体内评估了 PFKFB3 抑制剂 2E-3-(3-吡啶基)-1-(4-吡啶基)-2-丙烯-1-酮 (3PO) 对细胞存活、克隆形成、迁移的影响，使用结直肠癌细胞、患者来源的肿瘤类器官（PDO）和异种移植物（PDX）进行侵袭和代谢研究。 3PO 处理结直肠癌细胞可增加辐射诱导的细胞死亡并减少癌细胞侵袭。此外，基因集富集分析表明，3PO 能够改变 PDO 的代谢状态，使其发生氧化磷酸化。此外，体内新辅助治疗3PO诱导TVN，缓解肿瘤缺氧并增加肿瘤坏死。我们的结果支持 PFKFB3 抑制作为直肠癌患者未来可能的新辅助疗法。

Treatment of patients with locally advanced rectal cancer (RC) is based on neoadjuvant chemoradiotherapy followed by surgery. In order to reduce the development of therapy resistance, it is necessary to further improve previous treatment approaches. Recent in vivo experimental studies suggested that the reduction of tumor hypoxia by tumor vessel normalization (TVN), through the inhibition of the glycolytic activator PFKFB3 could significantly improve tumor response to therapy. We have evaluated in vitro and in vivo the effects of the PFKFB3 inhibitor 2E-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) on cell survival, clonogenicity, migration, invasion and metabolism using colorectal cancer cells, patient-derived tumor organoids (PDO) and xenografts (PDX). 3PO treatment of colorectal cancer cells increased radiation-induced cell death and reduced cancer cell invasion. Moreover, Gene Set Enrichment Analysis shows that 3PO is able to alter the metabolic status of PDOs towards oxidative phosphorylation. Additionally, in vivo neoadjuvant treatment with 3PO induced TVN, alleviated tumor hypoxia and increased tumor necrosis. Our results support PFKFB3 inhibition as a possible future neoadjuvant addition for rectal cancer patients.