瘤进化中的新兴趋势和收证据:综合性综述
Chenqi Jin1, Weiqi Li1, Boqiang Liu2
1Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Zhejiang 310016, PR China; Zhejiang Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang 310016, PR China.
概括
瘤进化是一个由遗传,表观遗传和微环境因素驱动的复杂过程,导致癌症的进展和治疗耐药性. 了解这些动态是开发适应性疗法的关键,这些疗法既针对癌细胞,也针对癌细胞及其生态系统.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 进化医学是一种进化医学.
背景情况:
- 瘤进化是一个时空过程,涉及遗传突变,表观遗传变化和微环境相互作用,推动癌症的进展,转移和抵抗.
- 基础模型 (线性,分支,中性,平行) 通过渐进的突变或基因组事件解释瘤多样化,其适用性取决于选择性压力.
- 身体突变作为谱系条形码,而表观遗传失调 (DNA甲基化,RNA修饰) 提供了表型可塑性,可以在没有DNA改变的情况下快速适应.
研究的目的:
- 阐明瘤进化的多方面的驱动因素,包括遗传,表观遗传和微环境因素.
- 突出瘤微环境作为癌细胞适应和异质性的动态编排者的作用.
- 强调需要先进的技术和综合模型来理解和打击瘤进化和治疗耐药性的需要.
主要方法:
- 在瘤多样化的背景下分析基础进化模型 (线性,分支,中性,平行).
- 作为非遗传异质性的驱动因素,对体突变和表观遗传失调 (DNA甲基化,RNA修饰) 的研究.
- 探索瘤微环境对癌细胞适应和空间选择压力的影响 (低氧,乳酸,神经交叉声).
- 利用新兴技术,如单细胞测序,空间多组学和液体活检来解码瘤内异质性和克隆动态.
主要成果:
- 瘤进化是由遗传,表观遗传和微环境因素的复杂相互作用形成的,导致表型多样性.
- 瘤微环境通过不同的生态和空间异质的选择压力,积极协调癌症的进化.
- 处理压力造成了进化瓶,选择了耐药克隆并促进了交叉耐药性.
- 新兴技术使瘤内异质性和克隆进化的实时,多维解码成为可能.
结论:
- 将进化模型与多omics数据集成对于理解瘤适应和开发临时适应性疗法至关重要.
- 目前的临床前模型需要进步,以准确地回顾人类瘤微环境相互作用的转化研究.
- 未来的个性化瘤学依赖于人工智能和纵向生物标志物分析,以超越静态基因组匹配和控制癌症演变.
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