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Page 8 of 11                             Chang et al. J Cancer Metastasis Treat 2019;5:78  I  http://dx.doi.org/10.20517/2394-4722.2019.31

               creating greater need for FACT activity? Do elevated transcription and replication decrease the stability
               of nucleosomes, or do tumor cells promote destabilization through an unknown mechanism to provide
               advantages such as easier reorganization of the three-dimensional structure of the genome or easier
               transitions among gene expression profiles? What is the relationship between nucleosome stability and
               three-dimensional chromatin structure? While it might seem obvious that loss of chromatin structure is
               disadvantageous, is this because of toxicity of the free histones that are produced by chromatin disassembly
               or is it the result of inappropriate exposure of DNA? Cancer cells survive by unleashing the beasts of
               excessive proliferation and metastasis that are normally constrained within chromatin; how do FACT and
               curaxins alter the balance between taking advantage of these dangerous forces to become cancerous and
               being overtaken by them?


               DECLARATIONS
               Authors’ contributions
               Wrote the initial draft of the manuscript and finalized it: Chang HW
               Wrote parts of the manuscript: Nizovtseva EV, Razin SV
               Wrote parts of the manuscript and prepared the final figures: Formosa T
               Wrote parts of the manuscript: Gurova KV
               Designed the review and the figures, wrote parts of the manuscript and finalized it: Studitsky VM

               Availability of data and materials
               Not applicable.

               Financial support and sponsorship
               This work was supported by the National Cancer Institute (R01CA197967 to Gurova KV and R21CA220151
               to Studitsky VM), the National Institute of General Medical Sciences (R01 GM119398 to Studitsky VM and
               R01 GM064649 to Formosa T), and by the Russian Science Foundation (19-74-30003).


               Conflicts of interest
               Gurova KV obtained a research grant and consulting payments from Incuron, Inc. The remaining authors
               declared that there are no conflicts of interest.


               Ethical approval and consent to participate
               Not applicable.

               Consent for publication
               Not applicable.


               Copyright
               © The Author(s) 2019.


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