OPEN BIO:癌症进化研究或可催生抗癌新疗法

2020-04-20 XJTLU 西交利物浦大学

以改变癌细胞进化的微环境为基础研发抗癌新疗法,极有可能兼具可行性与有效性。

以改变癌细胞进化的微环境为基础研发抗癌新疗法,极有可能兼具可行性与有效性。

如上是一项癌症进化理论研究的结果,该研究发表于英国皇家学会《开放生物学》期刊,很可能有助于开发更为精准的癌症预防手段和抗癌疗法。

西交利物浦大学生物科学系讲师姜小炜博士和英国癌症研究爱丁堡中心主任Ian Tomlinson教授共同完成了这项与多变的肿瘤微环境(TME)及其对人体内癌细胞数量增长的影响有关的研究。

姜博士表示,通过改变微环境消灭癌细胞可能有助于控制癌症发展。

长久以来,癌症的发育被视为一种达尔文生物进化过程,在此过程中,变化的肿瘤微环境很可能扮演了至关重要的角色。很多癌症建模研究都忽视了各种不同变化的肿瘤微环境究竟如何影响癌症进化。

我们建立了一个3D的数学模型来模拟变化的微环境下癌症的进化过程,得出了多种极为复杂的癌症适应性模式,并且预测到了和临床病例情况相似的肿瘤形态。

变化的肿瘤微环境对癌症适应性进化起阻碍作用,这在一定程度上解释了为什么癌症并不总会发生,且没有预期那么普遍。

为什么现实生活中的癌症病例比理论上的要少得多呢?——这是一个未解之谜。

虽然现在癌症并不少见,但是根据我们目前掌握的相关知识,实际出现的癌症病例是比预期的少很多的;结合基因突变率和正常细胞的数量,会发现其实每个人体内都可能存在多种癌症。

这种数量差异背后有几个可能的原因,包括人体对于癌症的免疫反应和固有的组织稳态维持机制,它们起到了“缓冲”的作用。

我们猜想还有另外一种因素阻碍了癌症的发展,那就是变化的肿瘤微环境。这种变化能削弱癌细胞的适应能力,使其无法发展为癌症。

和可以产生中性进化的静态微环境相比,变化的微环境会导致癌细胞产生带有时空上异质性的复杂适应性进化,涉及到驱动变异的变化不定的适应度效应、亚克隆混合、亚克隆竞争和不同系统发育模式。

很多情况下,癌细胞群体会停止生长或自行减少,甚至消除。

想象有一株向日葵生长在温室里,每天都在同个地方被阳光照射,它的成长应该是规律而均衡的。相比之下,如果有一量全速行驶的车,在拥挤的车后座上放一盆类似的向日葵,混杂在其他物品中,它开花的时间就不确定得多了。

原始出处:
Jiang X, Tomlinson IPM. 2020 Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anticancer therapy. Open Biol. 10: 190297.

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    2020-12-10 sunylz
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    2021-02-22 feather89
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    2020-04-22 kcb074

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