Science:结直肠癌对靶向疗法的适应性变异

2019-12-14 海北 MedSci原创

耐药性的出现限制了靶向疗法在人类肿瘤中的功效。现在大家普遍的看法是耐药是既成事实:开始治疗时,癌症已经含有耐药性突变细胞。

耐药性的出现限制了靶向疗法在人类肿瘤中的功效。现在大家普遍的看法是耐药是既成事实:开始治疗时,癌症已经含有耐药性突变细胞。暴露于抗生素的细菌会暂时增加其突变率(自适应变异性),从而提高了生存的可能性。

最近,研究人员调查了人类直肠癌CRC)细胞是否同样利用自适应变异性来规避治疗压力。

研究人员发现,表皮生长因子受体(EGFR/ BRAF的抑制会下调错配修复(MMR)和同源重组(HRDNA修复基因,同时在药物耐受性细胞中上调易错的聚合酶。

在治疗期间,源自患者的异种移植物和肿瘤标本中的MMR蛋白也下调。 EGFR / BRAF抑制可诱导DNA损伤,增加变异性并触发微卫星不稳定性。

因此,像单细胞生物一样,肿瘤细胞通过增强变异性来规避治疗压力。


原始出处:

Mariangela Russo et al. Adaptive mutability of colorectal cancers in response to targeted therapies. Science, 2019; DOI: 10.1126/science.aav4474


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    2019-12-16 jichang
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    2019-12-16 thm112988

    0

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    2019-12-15 txqjm

    谢谢了,学习

    0

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