Macropinocytosis is an evolutionarily conserved form of endocytosis that 
mediates non-selective uptake of extracellular fluid and the solutes contained 
therein. In mammalian cells, macropinocytosis is initiated by growth 
factor-mediated activation of the Ras and PI3-kinase signalling pathways. In 
malignant cells, oncogenic activation of growth factor signalling sustains 
macropinocytosis cell autonomously. Recent studies of cancer metabolism, 
discussed here, have begun to define a role for macropinocytosis as a nutrient 
uptake route. Macropinocytic cancer cells ingest macromolecules in bulk and 
break them down in the lysosome to support metabolism and macromolecular 
synthesis. Thereby, macropinocytosis allows cells to tap into the copious 
nutrient stores of extracellular macromolecules when canonical nutrients are 
scarce. These findings demonstrate that macropinocytosis promotes metabolic 
flexibility and resilience, which enables cancer cells to survive and grow in 
nutrient-poor environments. Implications for physiological roles of growth 
factor-stimulated macropinocytosis in cell metabolism and its relationship with 
other nutrient uptake pathways are considered. This article is part of the Theo 
Murphy meeting issue 'Macropinocytosis'.