Fig. 8: Interventions that alter the competitive fitness of oncogenic PIK3CA mutant clones.
From: Organismal metabolism regulates the expansion of oncogenic PIK3CA mutant clones in normal esophagus
Top: overactivation of the PI3K–mTOR pathway increases the competitive fitness of Pik3caH1047R/wt mutant over wild-type cells, by reducing mutant cell differentiation, which drives clonal expansion. Middle: interventions that level out the differential activation of the PI3K–mTOR axis and cell fitness between wild-type and mutant cells neutralize the competitive advantage of the mutants. Bottom: on the contrary, metabolic conditions such as type 1 diabetes and overweight would further increase the cellular differences in the PI3K–mTOR axis between both cell types, resulting in a further increase in the competitive fitness of the mutant over wild-type cells.
