Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Genes (Basel). 2023 Sep 24;14(10):1856. doi: 10.3390/genes14101856.
The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution.
癌症的发生发展始于细胞从多细胞状态向类似于单细胞生物的状态转变。这种转变导致多细胞性所固有的关键调节因子失活,从而产生具有增强适应性的不同癌细胞亚群。肿瘤内不同细胞亚群的存在,即肿瘤内异质性(ITH),给癌症治疗带来了挑战。在这篇综述中,我们深入探讨了癌症发生和进展过程中从多细胞性到单细胞性转变的动态。我们强调了遗传和非遗传因素以及肿瘤微环境在促进 ITH 和癌症演化中的作用。此外,我们还介绍了组学技术的最新进展,这些技术允许在单细胞水平上对肿瘤进行深入分析,并了解其在组织中的空间组织。获得这些详细信息对于加深我们对癌症多种进化途径的理解至关重要,从而可以开发针对癌症进化关键驱动因素的有效治疗方法。