In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.For unicellular organisms such as microbes, there is evolutionary pressure to reproduce as quickly as possible when nutrients are available. Their metabolic control systems have evolved to sense an adequate supply of nutrients and channel the requisite carbon, nitrogen, and free energy into generating the building blocks needed to produce a new cell. When nutrients are scarce, the cells cease biomass production and adapt metabolism to extract the maximum free energy from available resources to survive the starvation period (Fig. 1). Reflecting these fundamental differences in metabolic needs, distinct regulatory mechanisms have evolved to control cellular metabolism in proliferating versus non-proliferating cells.In multicellular organisms, most cells are exposed to a constant supply of nutrients. Survival of the organism requires control systems that prevent aberrant individual cell proliferation when nutrient availability exceeds the levels needed to support cell division. Uncontrolled proliferation is prevented because mammalian cells do not normally take up nutrients from their environment unless stimulated to do so by growth factors. Cancer cells overcome this growth factor dependence by acquiring genetic mutations that functionally alter receptorinitiated signaling pathways. There is growing evidence that some of these pathways constitutively activate the uptake and metabolism of nutrients that both promote cell survival and fuel cell growth (1,2). Oncogenic mutations can result in the uptake of nutrients,

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.