Mathematical models of cancer metabolism

Elke Katrin Markert, Alexei Vazquez

Metabolism is essential for life, and its alteration is implicated in multiple human diseases. The transformation from a normal to a cancerous cell requires metabolic changes to fuel the high metabolic demands of cancer cells, including but not limited to cell proliferation and cell migration. In recent years, there have been a number of new discoveries connecting known aberrations in oncogenic and tumour suppressor pathways with metabolic alterations required to sustain cell proliferation and migration. However, an understanding of the selective advantage of these metabolic alterations is still lacking. Here, we review the literature on mathematical models of metabolism, with an emphasis on their contribution to the identification of the selective advantage of metabolic phenotypes that seem otherwise wasteful or accidental. We will show how the molecular hallmarks of cancer can be related to cell proliferation and tissue remodelling, the two major physiological requirements for the development of a multicellular structure. We will cover different areas such as genome-wide gene expression analysis, flux balance models, kinetic models, reaction diffusion models and models of the tumour microenvironment. We will also highlight current challenges and how their resolution will help to achieve a better understanding of cancer metabolism and the metabolic vulnerabilities of cancers.