The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment

and prepare for metastasis. Qualitatively

the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells

but the cancer cells produce a local environment

the TME

that is hostile to the stromal cells

and compete for nutrients. In order to proliferate

cells need sufficient nutrients

either those that cannot be made by the cells themselves

or must be made from simpler precursors. However

in solid tumors

the nutrient supply is often limiting given the potential for rapid proliferation

and the poor quality of the vasculature. Thus

cancer cells may employ a variety of strategies to obtain nutrients for survival

growth and metastasis. Although much has been learned using established cell lines in standard culture conditions

it is becoming clear from in vivo metabolic studies that this can also be misleading

and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor

and even within the same tumor. Here we review the operation of metabolic networks

and how recent understanding of nutrient supply in the TME and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.