In tumour cells, macropinocytosis functions as an amino acid supply route and 
supports cancer cell survival and proliferation. Initially demonstrated in 
oncogenic KRAS-driven models of pancreatic cancer, macropinocytosis triggers the 
internalization of extracellular proteins via discrete endocytic vesicles called 
macropinosomes. The incoming protein cargo is targeted for lysosome-dependent 
degradation, causing the intracellular release of amino acids. These 
protein-derived amino acids support metabolic fitness by contributing to the 
intracellular amino acid pools, as well as to the biosynthesis of central carbon 
metabolites. In this way, macropinocytosis represents a novel amino acid supply 
route that tumour cells use to survive the nutrient-poor conditions of the 
tumour microenvironment. Macropinocytosis has also emerged as an entry mechanism 
for a variety of nanomedicines, suggesting that macropinocytosis regulation in 
the tumour setting can be harnessed for the delivery of anti-cancer 
therapeutics. A slew of recent studies point to the possibility that 
macropinocytosis is a pervasive feature of many different tumour types. In this 
review, we focus on the role of this important uptake mechanism in a variety of 
cancers and highlight the main molecular drivers of macropinocytosis in these 
malignancies. This article is part of the Theo Murphy meeting issue 
'Macropinocytosis'.