Mathematical Modeling of Field Cancerization through the Lens of Cancer Behavioral Ecology

Field cancerization is a process in which a normal tissue is replaced with pre-cancerous but histologically normal tissue. This transformed field can give rise to malignancy and contribute to tumor relapse. In this paper, we create a mathematical model of field cancerization from the perspective of cancer behavioral ecology. In our model, field cancerization arises from a breakdown in signaling integrity and control, and investigate implications for acute wounding, chronic wounding, aging, and therapeutic interventions. We find that restoration of communication networks can lead to cancer regression in the context of acute injury. Conversely, long term loss of controls, such as through chronic wounding or aging, can promote oncogenesis. These results are paralleled in therapeutic interventions: those that simply target cells in cancerous states may be less effective than those that reestablish signaling integrity. Viewing cancer as a corruption of communication systems rather than as a corruption of individual cells may lead to novel approaches for understanding and treating this disease.