Vargas-Rondón Natalia, Villegas Victoria E, Rondón-Lagos Milena
School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia.
Biology Program, Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia.
Cancers (Basel). 2017 Dec 28;10(1):4. doi: 10.3390/cancers10010004.
Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses.
癌症是主要的死亡原因之一，尽管近年来研究不断增加，但对晚期疾病的控制和最佳治疗反应仍然难以捉摸。最近的技术进步增进了我们对人类癌症这种异质性疾病的理解。例如，最近新增了癌症的四个特征，这些特征除了参与癌症发展外，还可能与治疗反应和耐药性有关。其中一个特征是染色体不稳定（CIN），它是染色体数目或结构改变导致的遗传变异来源。近年来，CIN已成为一个热门话题，不仅因为它在癌症诊断和预后中的意义，还因为它在治疗反应中的作用。染色体改变主要用于确定肿瘤中的遗传异质性，但CIN也可以揭示治疗效果，因为许多疗法都是基于增加CIN，从而导致异常细胞发生凋亡。然而，应该注意的是，关于CIN对治疗反应的影响存在相互矛盾的研究结果，一些研究将高CIN与更好的治疗反应相关联，而另一些研究则将其与治疗耐药性相关联。考虑到这些观察结果，有必要增进我们对CIN不仅在肿瘤发展中，而且在治疗反应中所起作用的理解。本综述重点关注最近的研究，这些研究提示了CIN在不同疾病类型中的可能机制和后果，主要关注癌症结局和治疗反应。
