Pantziarka Pan
The George Pantziarka TP53 Trust , London , United Kingdom.
PeerJ. 2016 Jun 29;4:e2176. doi: 10.7717/peerj.2176. eCollection 2016.
While there have been enormous advances in our understanding of the genetic drivers and molecular pathways involved in cancer in recent decades, there also remain key areas of dispute with respect to fundamental theories of cancer. The accumulation of vast new datasets from genomics and other fields, in addition to detailed descriptions of molecular pathways, cloud the issues and lead to ever greater complexity. One strategy in dealing with such complexity is to develop models to replicate salient features of the system and therefore to generate hypotheses which reflect on the real system. A simple tumour growth model is outlined which displays emergent behaviours that correspond to a number of clinically relevant phenomena including tumour growth, intra-tumour heterogeneity, growth arrest and accelerated repopulation following cytotoxic insult. Analysis of model data suggests that the processes of cell competition and apoptosis are key drivers of these emergent behaviours. Questions are raised as to the role of cell competition and cell death in physical cancer growth and the relevance that these have to cancer research in general is discussed.
尽管近几十年来我们对癌症相关的基因驱动因素和分子途径的理解取得了巨大进展,但在癌症的基本理论方面仍存在关键争议领域。除了对分子途径的详细描述外,基因组学和其他领域大量新数据集的积累使问题变得模糊,并导致了更大的复杂性。应对这种复杂性的一种策略是开发模型来复制系统的显著特征,从而生成反映真实系统的假设。本文概述了一个简单的肿瘤生长模型,该模型展示了与多种临床相关现象相对应的涌现行为,包括肿瘤生长、肿瘤内异质性、生长停滞以及细胞毒性损伤后的加速再增殖。对模型数据的分析表明,细胞竞争和凋亡过程是这些涌现行为的关键驱动因素。本文提出了关于细胞竞争和细胞死亡在实体肿瘤生长中的作用问题,并讨论了这些问题对癌症研究总体的相关性。