Figure 1. The Hallmarks of Cancer.

In addition to the six hallmarks originally proposed by Hanahan and Weinberg (top half, white symbols) and evasion of immune surveillance proposed by Kroemer and Pouyssegur, we propose a set of additional hallmarks that depict the stress phenotypes of cancer cells (lower half, colored symbols). These include metabolic stress, proteotoxic stress, mitotic stress, oxidative stress, and DNA damage stress. Functional interplays among these hallmarks promote the tumorigenic state and suppress oncogenic stress. For example, the utilization of glycolysis allows tumor cells to adapt to hypoxia and acidify its microenvironment to evade immune surveillance. Increased mitotic stress promotes aneuploidy, which leads to proteotoxic stress that requires compensation from the heat shock response pathway. Elevated levels of reactive oxygen species result in increased levels of DNA damage that normally elicits senescence or apoptosis but is overcome by tumor cells.