阿德莱德大学研究发现癌细胞可能特别容易发生代谢应激，这就有助于在不伤害正常细胞的情况下开发新的靶向治疗。

研究人员发现染色体不稳定性(这是快速分裂癌细胞的标志)使癌细胞发生应激，易受轻度代谢受阻。新陈代谢是机体正常的过程，能够将食物转化为能量。论文主要作者Stephen Gregory博士说：治疗癌症的一个共同问题是，癌症不回应化疗，或一段时间响应之后再复发。

发生这种情况的一个原因是因为肿瘤通常不是由完全相同的细胞组成的，而是由多样化细胞构成的，并且这些细胞是实时变化的。在癌细胞分裂时有时会失去、有时会获得染色体，这种现象即所谓的染色体不稳定。染色体不稳定有助癌细胞抵抗化疗药物。

研究表明，染色体不稳定性对于癌细胞有一定影响，癌细胞发生代谢应激后只需要一个小的代谢干扰策略就能杀死他们。目前化疗对于所有分裂的细胞毒性也很大，特别是影响到毛囊，肠壁和血液中的细胞，往往会造成患者脱发，疼痛和不适。我们需要找到方法来瞄准癌细胞，而不会影响其他正常分裂的细胞。研究者诱导小型实验果蝇发生染色体不稳定，结果发现染色体不稳定细胞特别容易发生代谢应激。

Gregory博士说：这意味着我们能够开发出对患者没有任何副作用，而且能够杀死染色体不稳定肿瘤细胞的治疗方法。该研究成果已经发表在Oncogene杂志上。

原文摘要：

Chromosomal instABIlity causes sensitivity to metabolic stress.

Shaukat Z, Liu D, Choo A,et al.

Chromosomal INstability (CIN), a hallmark of cancer, refers to cells with an increased rate of gain or loss of whole chromosomes or chromosome parts. CIN is linked to the progression of tumors with poor clinical outcomes such as drug resistance. CIN can give tumors the diversity to resist therapy, but it comes at the cost of significant stress to tumor cells. To tolerate this, cancer cells must modify their energy use to provide adaptation against genetic changes as well as to promote their survival and growth. In this study, we have demonstrated that CIN induction causes sensitivity to metabolic stress. We show that mild metabolic disruption that does not affect normal cells, can lead to high levels of oxidative stress and subsequent cell death in CIN cells because they are already managing elevated stress levels. Altered metabolism is a differential characteristic of cancer cells, so our identification of key regulators that can exploit these changes to cause cell death may provide cancer-specific potential drug targets, especially for advanced cancers that exhibit CIN.Oncogene advance online publication, 27 October 2014; doi:10.1038/onc.2014.344.

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