Self-renewal of tumor cells: epigenetic determinants of the cancer stem cell phenotype

Among the functional subpopulations that coexist within the tumor, 'cancer stem cells' are characterized by increased self-renewal and the ability to derive all of the other subpopulations of tumor cells ('bulk'). The functional heterogeneity among cancer stem cells and bulk cells must reflect distinct cellular epigenetic landscapes, but - due to the difficulty to isolate bona fide cancer stem cells with a high degree of purity - those different epigenetic landscapes, and the molecular mechanisms underlying them, remain largely unknown. Cues of intratumor phenotypic plasticity complicate the interpretation of the cancer stem cell phenotype: we contend that, however, the concept of cancer stem cell has crucial therapeutic implication, and remains a key target for the exploration of the cancer epigenome.