Integrative physical oncology

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.