Skip to main content
. Author manuscript; available in PMC: 2013 Dec 1.
Published in final edited form as: Free Radic Biol Med. 2012 Sep 26;53(11):2178–2187. doi: 10.1016/j.freeradbiomed.2012.09.028

Figure 7. Integrating metabolic defects into the epigenetic progenitor model of the origins of cancer.

Figure 7

We can operationally divide the origins of cancer into three discrete steps: creation of metabolic changes, formation of founding epigenetic events, and cancer progression. Metabolic changes are created through alterations in the cellular microenvironment. These in turn limit the availability of cofactors to epigenetic enzymes. Aberrant epigenetic events can be created that silence tumor suppressor genes (TSG) and activate oncogenes (ONC) and thus creating founding epigenetic events in an epigenetic progenitor. As the epigenetic progenitor clonally expands at an accelerated rate additional changes occur in cellular metabolism to form epigenetic plasticity. The clonogen can expand further and acquire additional mutations to cause cancer progression and manifest the malignant phenotype.