Natalya N. Pavlova1 and Craig B. Thompson2 1Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA 2Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA Correspondence: natasha.pavlovahci.utah.edu

A cell committed to proliferation must reshape its metabolism to enable robust yet balanced production of building blocks for the assembly of proteins, lipids, nucleic acids, and other macromolecules, from which two functional daughter cells can be produced. The metabolic remodeling associated with proliferation is orchestrated by a number of pro-proliferative signaling nodes, which include phosphatidylinositol-3 kinase (PI3K), the RAS family of small GTPases, and transcription factor c-myc. In metazoan cells, these signals are activated in a paracrine manner via growth factor–mediated activation of receptor (or receptor-associated) tyrosine kinases. Such stimuli are limited in duration and therefore allow the metabolism of target cells to return to the resting state once the proliferation demands have been satisfied. Cancer cells acquire activating genetic alterations within common pro-proliferative signaling nodes. These alterations lock cellular nutrient uptake and utilization into a perpetual progrowth state, leading to the aberrant accumulation and spread of cancer cells.