Douglas Hanahan, Robert A. Weinberg. Hallmarks of cancer: the next generation. Cell, Volume 144, Issue 5, p646–674, 4 March 2011
We have defined the hallmarks of cancer as acquired functional capabilities that allow cancer cells to survive, proliferate, and disseminate; these functions are acquired in different tumor types via distinct mechanisms and at various times during the course of multistep tumorigenesis. Their acquisition is made possible by two enabling characteristics. Most prominent is the development of genomic instability in cancer cells, which generates random mutations including chromosomal rearrangements; among these are the rare genetic changes that can orchestrate hallmark capabilities. A second enabling characteristic involves the inflammatory state of premalignant and frankly malignant lesions that is driven by cells of the immune system, some of which serve to promote tumor progression through various means.
Yet other distinct attributes of cancer cells have been proposed to be functionally important for the development of cancer and might therefore be added to the list of core hallmarks. Two such attributes are particularly compelling. The first involves major reprogramming of cellular energy metabolism in order to support continuous cell growth and proliferation, replacing the metabolic program that operates in most normal tissues and fuels the physiological operations of the associated cells. The second involves active evasion by cancer cells from attack and elimination by immune cells; this capability highlights the dichotomous roles of an immune system that both antagonizes and enhances tumor development and progression. Both of these capabilities may well prove to facilitate the development and progression of many forms of human cancer and therefore can be considered to be emerging hallmarks of cancer. These enabling characteristics and emerging hallmarks, depicted in Figure 3, are discussed individually below.