Therapeutic Targeting of Tumor Metabolism
Dr. Fátima Martel E-Mail
Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Metabolic remodeling is a key feature of cancer cells. In order to support their high rates of proliferation, cancer cells consume additional nutrients and divert those nutrients into macromolecular synthesis pathways. Metabolic pathways must therefore be rewired in such a way that balances biosynthetic processes with sufficient ATP production to support cell growth and survival. As all cancer cells are dependent on this change in metabolism, these altered pathways represent attractive therapeutic targets.
Knowledge of cancer cell metabolic characteristics has greatly expanded since the first observation of abnormal glucose metabolism in cancer cells, the so-called Warburg effect. Currently, a complex set of changes in macronutrient (carbohydrates, amino acids, and lipids) metabolism is known to exist in cancer cells. It is also evident that many of the signaling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism. Moreover, spatial heterogeneity of nutrient availability and metabolic phenotypes exists, allowing metabolic cooperation between different populations of cells within tumors. It is also of note that some anticancer therapy agents (eg. antifolates) target the specific metabolic needs of cancer cells and remain effective agents in the clinic today.
Targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice. Not only it is important to explore the possibility of targeting metabolic dependencies of cancer cells as a selective anticancer strategy, and identifying tumors susceptible to metabolic therapy, but it is also crucial to understand and explore altered metabolic phenotypes of therapy-resistant tumors, relative to treatment-naïve tumors, as a target to overcome cancer resistance to therapy.
Keywords: Cancer metabolism; carbohydrate; amino acid; lipid; therapy