Abstract
Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing cells assume new phenotypes while jettisoning older behaviors. The lack of a systemic understanding of this complex phenomenon has limited progress in developing treatments for metastatic disease. Because metastasis has traditionally been investigated in distinct physiological compartments, the integration of these complex and interlinked aspects remains a challenge for both systems-level experimental and computational modeling of metastasis. Here, we present some of the current perspectives on the complexity of cancer metastasis, the multiscale nature of its progression,and a systems-level view of the processes underlying the invasive spread of cancer cells. We also highlight the gaps in our current understanding of cancer metastasis as well as insights emerging from interdisciplinary systems biology approaches to understand this complex phenomenon.
Highlights
IntroductionThe processes involving dissemination of cancer cells from a primary lesion to distal organs, is the principal cause of cancer lethality
Cancer metastasis, the processes involving dissemination of cancer cells from a primary lesion to distal organs, is the principal cause of cancer lethality
We present some of the current perspectives on the complexity of cancer metastasis, the multiscale nature of its progression, and a systems-level view of the processes underlying the invasive spread of cancer cells
Summary
The processes involving dissemination of cancer cells from a primary lesion to distal organs, is the principal cause of cancer lethality. Understanding the complex interactions between cancer cells and the tumor microenvironment that lead to metastasis will require integration of extensive molecular characterization data collected from in vitro and in vivo experimental models. Systems Approaches to Studying Metastasis Understanding how the complex molecular-level behavior of cancer cells and their interactions with the tumor microenvironment lead to metastasis will require the integration of physiological metastasis models and extensive phenotypic and molecular characterization. Individual models constructed at one scale (for example, a static picture of gene regulatory networks operating within a cell, the dynamic simulation of a signaling pathway promoting cell motility, or the spatial representation of invasion of cancer cells into the stroma) will need to be integrated into a multiscale framework representative of a systems understanding of metastasis. A comprehensive model of the phosphoinositide pathway could contribute to the
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