Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
Wiley Interdiscip Rev Syst Biol Med. 2012 Jan-Feb;4(1):1-14. doi: 10.1002/wsbm.158. Epub 2011 Aug 18.
Cancer is arguably the ultimate complex biological system. Solid tumors are microstructured soft matter that evolves as a consequence of spatio-temporal events at the intracellular (e.g., signaling pathways, macromolecular trafficking), intercellular (e.g., cell-cell adhesion/communication), and tissue (e.g., cell-extracellular matrix interactions, mechanical forces) scales. To gain insight, tumor and developmental biologists have gathered a wealth of molecular, cellular, and genetic data, including immunohistochemical measurements of cell type-specific division and death rates, lineage tracing, and gain-of-function/loss-of-function mutational analyses. These data are empirically extrapolated to a diagnosis/prognosis of tissue-scale behavior, e.g., for clinical decision. Integrative physical oncology (IPO) is the science that develops physically consistent mathematical approaches to address the significant challenge of bridging the nano (nm)-micro (µm) to macro (mm, cm) scales with respect to tumor development and progression. In the current literature, such approaches are referred to as multiscale modeling. In the present article, we attempt to assess recent modeling approaches on each separate scale and critically evaluate the current 'hybrid-multiscale' models used to investigate tumor growth in the context of brain and breast cancers. Finally, we provide our perspective on the further development and the impact of IPO.
癌症可以说是最复杂的生物系统。实体瘤是微结构的软物质,它是细胞内(例如信号通路、大分子运输)、细胞间(例如细胞间粘附/通讯)和组织(例如细胞-细胞外基质相互作用、机械力)时空事件的结果而演变的。为了深入了解,肿瘤和发育生物学家收集了大量的分子、细胞和遗传数据,包括细胞类型特异性分裂和死亡率的免疫组织化学测量、谱系追踪以及功能获得/丧失突变分析。这些数据被经验性地外推到组织尺度行为的诊断/预后,例如用于临床决策。综合肿瘤物理学(IPO)是一门发展物理一致的数学方法的科学,旨在解决与肿瘤发展和进展有关的从纳米(nm)-微米(µm)到宏观(mm、cm)尺度的重大挑战。在当前的文献中,这种方法被称为多尺度建模。在本文中,我们试图评估每个单独尺度上的最新建模方法,并批判性地评估当前用于研究脑癌和乳腺癌中肿瘤生长的“混合多尺度”模型。最后,我们提供了我们对 IPO 的进一步发展和影响的看法。