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

Int J Mol Sci. 2019 Dec 29;21(1):240. doi: 10.3390/ijms21010240.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Cellular Reprogramming / genetics*
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation
  • Gene Order
  • Genome
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Thermodynamics*

Substances

  • Chromatin