结直肠癌对向治疗的适应性变异性
Mariangela Russo1,2, Giovanni Crisafulli3,2, Alberto Sogari3,2
1Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO) 10060, Italy. alberto.bardelli@unito.it mariangela.russo@unito.it.
概括
就像细菌一样, 结肠直肠癌细胞可以增加它们的突变率, 这种由DNA修复基因下调驱动的适应性可变性有助于瘤逃避治疗.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 抗药性是癌症治疗的一个主要挑战,
- 适应性可变性,即有机体在压力下增加突变率,在细菌中已知,但在人类癌症中不太了解.
研究的目的:
- 研究人类结肠直肠癌 (CRC) 细胞是否利用适应性可变性来逃避向治疗.
- 了解CRC治疗诱导的变异性背后的分子机制.
主要方法:
- 在CRC细胞中抑制表皮生长因子受体 (EGFR) / BRAF通路.
- 对DNA修复基因表达的分析 (不匹配修复和同源重组).
- 在耐药细胞和患者衍生的异种移植中评估DNA损伤,突变率和微卫星不稳定性.
主要成果:
- 抑制EGFR/ BRAF导致了DNA修复基因的下调和易发生错误的聚合酶的上调.
- 在治疗期间,患者衍生的异种移植和瘤样本中的MMR蛋白水平下降.
- 向治疗诱导了DNA损伤,增加了细胞可变性,并引发了微卫星的不稳定性.
结论:
- 人类结直肠癌细胞可以增强其可变性以逃避治疗压力,类似于单细胞生物.
- 适应性可变性是癌症抗药的一个新机制, 需要进一步研究.
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