We once proposed that cell-type-associated chromatin configurations determine cell types and that cancer cell type is determined by cancer-associated chromatin configuration (CACC). In this paper, we hypothesize that flexible cell-type-associated chromatin configuration is associated with cell potency and has an advantage over inflexible one in regulating genome related activities, such as DNA replication, DNA transcription, DNA repair, and DNA mutagenesis. The reason why cancer is so difficult to treat is because CACC is flexible, which enables cancer cells not only to produce heterogeneous subclones through limited cell differentiation, but also to maximally and efficiently use genome related resources to survive environmental changes. Therefore, to beat cancer, more efforts should be made to restrict the flexibility of CACC or to change CACC so that cancer cells can be turned back to normal or become less malignant.
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