{Reference Type}: Journal Article {Title}: Exploiting cancer's drinking problem: regulation and therapeutic potential of macropinocytosis. {Author}: Puccini J;Badgley MA;Bar-Sagi D; {Journal}: Trends Cancer {Volume}: 8 {Issue}: 1 {Year}: 01 2022 {Factor}: 19.161 {DOI}: 10.1016/j.trecan.2021.09.004 {Abstract}: Macropinocytosis, an evolutionarily conserved endocytic mechanism that mediates non-specific fluid-phase uptake, is potently upregulated by various oncogenic pathways. It is now well appreciated that high macropinocytic activity is a hallmark of many human tumors, which use this adaptation to scavenge extracellular nutrients for fueling cell growth. In the context of the nutrient-scarce tumor microenvironment, this process provides tumor cells with metabolic flexibility. However, dependence on this scavenging mechanism also illuminates a potential metabolic vulnerability. As such, there is a great deal of interest in understanding the molecular underpinnings of macropinocytosis. In this review, we will discuss the most recent advances in characterizing macropinocytosis: the pathways that regulate it, its contribution to the metabolic fitness of cancer cells, and its therapeutic potential.