A filter-flow perspective of haematogenous metastasis offers a non-genetic paradigm for personalised cancer therapy

Abstract

Research into mechanisms of haematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of ‘seed–soil’ relationships. Preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulation. Patterns of metastatic spread have been previously quantified using the metastatic efficiency index, a measure quantifying metastatic incidence for a given primary-target organ pair and the relative blood flow between them. We extend this concept to take into account the reduction in CTCs which occurs in organ capillary beds connected by a realistic vascular network topology. Application to a dataset of metastatic incidence reveals that metastatic patterns depend strongly on assumptions about the existence and location of micrometastatic disease which governs CTC dynamics on the network, something which has heretofore not been considered – an oversight which precludes our ability to predict metastatic patterns in individual patients