Department of Medicine, Massachusetts General Hospital, 32 Fruit Street, Yawkey 7B, Boston, Massachusetts 02114, USA.
Nat Rev Clin Oncol. 2018 Feb;15(2):81-94. doi: 10.1038/nrclinonc.2017.166. Epub 2017 Nov 8.
Cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). Heterogeneity provides the fuel for resistance; therefore, an accurate assessment of tumour heterogeneity is essential for the development of effective therapies. Multiregion sequencing, single-cell sequencing, analysis of autopsy samples, and longitudinal analysis of liquid biopsy samples are all emerging technologies with considerable potential to dissect the complex clonal architecture of cancers. In this Review, we discuss the driving forces behind intratumoural heterogeneity and the current approaches used to combat this heterogeneity and its consequences. We also explore how clinical assessments of tumour heterogeneity might facilitate the development of more-effective personalized therapies.
癌症是一种动态疾病。在疾病过程中，癌症通常变得更加异质性。由于这种异质性，大块肿瘤可能包含不同分子特征的不同细胞的多样性集合，对治疗的敏感性不同。这种异质性可能导致肿瘤细胞遗传上不同的亚群在疾病部位（空间异质性）或癌细胞分子组成的时间变化（时间异质性）的不均匀分布。异质性为耐药性提供了动力；因此，准确评估肿瘤异质性对于开发有效的治疗方法至关重要。多区域测序、单细胞测序、尸检样本分析和液体活检样本的纵向分析都是具有巨大潜力的新兴技术，可以剖析癌症复杂的克隆结构。在这篇综述中，我们讨论了肿瘤内异质性的驱动力以及目前用于对抗这种异质性及其后果的方法。我们还探讨了如何通过对肿瘤异质性的临床评估来促进更有效的个体化治疗的发展。
