Metabolic activity grows in human cancers pushed by phenotypic variability

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 (SUVmax), 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 SUVmax scales superlinearly with the mean metabolic activity (SUVmean), reflecting a dynamic preferential accumulation of activity on the hotspot. Additionally, SUVmax 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. [Display omitted] •The metabolic hotspot in human cancers becomes more active as tumors grow•Hotspot activity grows faster than the rest of the tumor and promotes heterogeneity•A mathematical model capturing phenotypic transitions reproduces the patient data•Non-genetic changes may suffice to fuel these increases in tumor metabolic activity Human metabolism; Mathematical biosciences; Cancer systems biology; Cancer