Nat Commun:5-FU激活WNT/β-catenin通路,促进结直肠癌的干性

2020-10-24 MedSci原创 MedSci原创

5-FU治疗的临床获益往往是短暂的,大多数治疗患者并没有实现肿瘤细胞的完全根除,导致5-FU治疗后复发而导致不良后果。

结直肠癌(CRC)是全世界最常见的癌症之一。尿嘧啶的氟化类似物5-氟尿嘧啶(5-FU)是CRC的姑息和辅助治疗化疗药物的基本成分。然而,5-FU治疗的临床获益往往是短暂的,大多数治疗患者并没有实现肿瘤细胞的完全根除,导致5-FU治疗后复发而导致不良后果。

以5-FU为基础的疗法,如FOLFOX(5-FU、亮丙瑞林和奥沙利铂)或FOLFIRI(5-FU、亮丙瑞林和伊立替康),已被作为晚期CRC5的标准疗法。虽然以5-FU为基础的治疗方法使CRC患者的客观反应率提高到40-50%,但CRC患者的无病生存期并未得到有效延长。因此,提高5-FU治疗的临床效果的策略是迫切需要的,了解5-FU治疗CRC患者复发的机制是提高5-FU为基础的CRC治疗生存获益的重要一步。

最近,研究人员在Nature Communications杂志发文,证明p53促进WNT3转录,导致ApcMin/+/Lgr5EGFP小鼠、CRC患者源性肿瘤类器官(PDTOs)和患者源性肿瘤细胞(PDCs)中WNT/β-catenin通路的激活。通过这种调节,5-FU诱导残余肿瘤中癌症干细胞(CSCs)的激活和富集,有助于治疗后的复发。

WNT抑制剂和5-FU的联合治疗有效地抑制了CSCs,减少了停止治疗后的肿瘤再生长。

这些研究结果表明p53是5-FU通过WNT/β-catenin信号通路诱导CSC激活的关键介质,并强调了WNT抑制剂和5-FU联合治疗的意义,是一种引人注目的治疗策略,可以改善目前5-FU为基础的疗法对CRC患者的不良结果

 

原始出处:

Yong-Hee Cho et al. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nature Communications (2020). 

 

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    2021-04-21 liye789132251
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    2021-03-21 马新雨

    学习了,5-fu治疗CRC复发机制

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    2020-10-26 zhwj

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