Determinants for how metabolism supports cancer progression

Abstract

Cells adapt metabolism to meet distinct physiological needs, and metabolic regulation influences tumor initiation and progression. To proliferate, cancer cells must adapt metabolism to support anabolic processes that allow the accumulation of biomass. The role metabolism plays in supporting cell growth and proliferation will be discussed. Recent work to identify the metabolic pathways that are most limiting for the proliferation of cancer cells in different environmental and tissue contexts will also be presented.
We find that nucleotide synthesis is often limiting, and how cells generate nucleotides is dictated by the tissue environment and tumor cell of origin, as well as by the initiating genetic mutations. For many tumors, access to oxygen or other electron acceptors limits the production of purines and pyrimidines. Analysis of metabolism in animal cancer models suggests that tumors can use different nutrients to allow tumor growth. Altering culture conditions in vitro can recapitulate some of the metabolic phenotypes observed in tumors, and these studies are providing insight into the factors that determine metabolic differences across different contexts. Manipulating whole body animal metabolism can also affect cancer outcomes and influence tumor progression and consideration of how whole body metabolism influences cancer cell metabolism will also be discussed.