Metabolic transformation in cancer

Abstract

In 2000, Douglas Hanahan and Robert Weinberg published a review detailing the six hallmarks of cancer. These are six phenotypes that a tumour requires in order to become a fully fledged malignancy: persistent growth signals, evasion of apoptosis, insensitivity to anti-growth signals, unlimited replicative potential, angiogenesis and invasion and metastasis. However, it is becoming increasingly clear that these phenotypes do not portray the whole story and that other hallmarks are necessary: one of which is a shift in cellular metabolism. The tumour environment creates a unique collection of stresses to which cells must adapt in order to survive. This environment is formed by the uncontrolled proliferation of cells, which ignore the cues that would create normal tissue architecture. As a result, the cells forming the tumour are exposed to low oxygen and nutrient levels, as well as high levels of toxic cellular waste products, which is thought to propel cells towards a more transformed phenotype, resistant to cell death and pro-metastatic.