Directed migration of cancer cells: a systems biophysics perspective

Directed migration of cancer cells is crucial to tumor progression, including tumorigenesis and metastasis. During migration, cancer cells encounter complex environmental cues and must process these signals to determine their migration direction. These cues include chemical, mechanical, and fluidic signals that vary across space and time. Although cancer cell migration has been extensively studied and many molecular regulators and signaling pathways have been identified, this molecular knowledge alone is often insufficient to predict migratory behavior in the highly heterogeneous tumor microenvironment. In this perspective, we present a systems biophysics framework that views directed migration as an information-processing problem constrained by the physics of cellular motion. Within this framework, a migrating cancer cell can be conceptualized as an integrated system composed of interacting subsystems responsible for information acquisition, information processing, and actuation. These subsystems collectively enable cells to sense environmental cues, process competing signals, and generate directed movement. Using a combination of biophysical analysis, experiments, and theoretical modeling, we discuss recent efforts to quantify fundamental sensing limits, characterize individual and collective information acquisition, investigate the capacity of cellular signal-processing machinery, and identify physical constraints governing migration accuracy and persistence. We further describe how minimal theoretical models and reverse-engineering approaches can reproduce key features of cellular decision-making, including the use of logic-gate-like behavior to process multiple environmental cues. Together, these studies illustrate how systems-level biophysical analysis can provide predictive insights into how cancer cells navigate complex microenvironments and may help establish a unified framework for understanding directed migration across diverse cellular systems.