Metabolic activity grows in human cancers pushed by phenotypic variability
Jesús J. Bosque, Gabriel F. Calvo, David Molina-García, Julián Pérez-Beteta, Ana María García Vicente, Víctor M. Pérez‐García
Abstract
Different evolutionary processes push cancers to increasingly aggressive behaviors, energetically sustained by metabolic reprogramming. The collective signature emerging from this transition is macroscopically displayed by positron emission tomography (PET). In fact, the most readily PET measure, the maximum standardized uptake value (SUV max ), has been found to have prognostic value in different cancers. However, few works have linked the properties of this metabolic hotspot to cancer evolutionary dynamics. Here, by analyzing diagnostic PET images from 512 patients with cancer, we found that SUV max scales superlinearly with the mean metabolic activity (SUV mean ), reflecting a dynamic preferential accumulation of activity on the hotspot. Additionally, SUV max increased with metabolic tumor volume (MTV) following a power law. The behavior from the patients data was accurately captured by a mechanistic evolutionary dynamics model of tumor growth accounting for phenotypic transitions. This suggests that non-genetic changes may suffice to fuel the observed sustained increases in tumor metabolic activity.