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. 2019 Dec 29;21(1):240.
doi: 10.3390/ijms21010240.

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Free PMC article

Resolution of Complex Issues in Genome Regulation and Cancer Requires Non-Linear and Network-Based Thermodynamics

Jekaterina Erenpreisa et al. Int J Mol Sci. .
Free PMC article


The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in biomedicine, requires complementation with a more systemic/holistic approach, to address the huge problem of cross-talk between more than 20,000 protein-coding genes, about 100,000 protein types, and the multiple layers of biological organization. In this perspective, the relationship between the chromatin network organization and gene expression regulation plays a fundamental role. The elucidation of such a relationship requires a non-linear thermodynamics approach to these biological systems. This change of perspective is a necessary step for developing successful 'tumour-reversion' therapeutic strategies.

Keywords: cancer resistance to drugs; cancer reversion therapy; chromatin network; genome positional information; reprogramming; self-organisation; transcription speciation.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Euchromatic and heterochromatic chromosome regions and their spatial separation in the nucleus. (a) Euchromatin (EC) and heterochromatin (HC) domains revealed by different approaches showing the principal components and differential replication timing. (b) EC resides in the nuclear interior, whereas HC localizes to the nuclear and nucleolar periphery. A scheme is republished from [14], Figure 1, with the licence provided by Elsevier and Copyright Centre.

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