高剂量放化疗对肿瘤或起反作用

yinfuhua

高剂量放化疗对肿瘤或起反作用' K) P( l& g' m
来源：科技日报 / 作者： / 2015-11-25
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为迅速清除肿瘤细胞，医学界通常采用化疗、放疗等杀伤性较强的治疗方法。近日，中国科学院北京基因组研究所与芝加哥大学合作，通过对肝癌的蜂窝式取样和深度基因测序的数据分析发现，肿瘤细胞群体内部的遗传多样性水平远远大于预期。这表明以身体最大承受力为基准的高剂量放化疗，不但会失效，甚至会助长抗性克隆的膨胀和发展，相关研究近日在线发表在《美国国家科学院院刊》上。0 `1 [' s+ P2 q+ p! V) H" _
肿瘤内部异质性通常是癌症产生抗药性、转移性的主要原因之一。精准医学让公众对其治愈肿瘤寄予厚望，然而研究人员通过建立模型发现，传统观念低估了具有上亿细胞数量的肿瘤内部的遗传异质性和顽强性，这使得人们需要重新系统认识肿瘤内部的遗传多样性、空间分布以及肿瘤转移和抗性产生的能力。5 |* |$ t& P9 X: ^2 v2 _
研究人员通过中性模型估算，一个直径约3.5厘米的肿瘤中携带了上亿个基因编码区的突变，高出以往的估算值几千倍。中科院北京基因组所凌少平博士介绍，放化疗的治疗方法可能杀死大部分癌细胞使得肿瘤中的主要细胞群体（克隆）被极大地削弱，但是由于更多的突变存在于未被杀死的微小癌细胞克隆，这使得具有特异突变的癌细胞存活下来，脱离了其他主要克隆在资源上的控制，使其以“野火烧不尽，春风吹又生”的增殖形成新的抗性肿瘤（转移或复发）。$ G. o3 ^/ v+ I' b, {6 `) p, i
该研究首次刻画出肿瘤的空间克隆结构，还揭示了肿瘤细胞巨大的遗传多样性远超出达尔文进化过程的估计。中科院北京基因组所吕雪梅研究员表示，由于肿瘤发生本质上是进化过程，进化遗传学和临床医学的交叉会给肿瘤临床医学带来更多的启示和解答。' Y' Y; X  ^$ ~7 p; b4 f8 M

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yaxiao5708

跟农药和抗生素一样，用多了就是抗药性，强制筛选出特异品种，而化疗、放疗之后的身体虚弱，更加助涨了癌细胞的发展壮大。

embryonic12

求原文，标题也行。

embryonic12

Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution1 M+ J' C' g5 \
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The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 “polymorphic” SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.

goblinwang

局部放疗，增强剂量，效果还是有的