Tuesday, 26 November 2019

Cancer-Chaotic oncogenic mutation-Epigenomic Alteration-Phase Transition-Metastasis

Hypothesis of Cancer:

1.Probably the epigenome of a cell is modified by an oncogenic mutation. Phenotypic plasticity/tumor heterogeneity occurs in this process.
2. This modified epigenome overrides the inhibitory signaling of tumor microenvironment. Chaos ensues.
3. The above (2) breaks cell cell interactions leading to tumor cells release from primary site and spread i.e. invasion.
4. Altered epigenome leads to epithelial mesenchymal transition.
5. Tumor cells at secondary site  undergo mesenchymal epithelial transition due to restored epigenome in a new microenvironment.
6. As critical threshlod of oncogenic protein/signaling activity is breached (1) happens again.
7. A vicious cycle of tumor growth and spread ensues.
8. Altered expression/phenotype of tumor cells  containing oncogenic mutation occurs via phase transition.
9. The unpredictable component is how the epigenome is altered from a normal one to a cancerous one via the  oncogenic mutation.

Analogy with an Enzymatic Reaction:

Initiator-Oncogenic mutation, Epigenome alteration/Ist hit
Catalyst-Altered Tumor Microenvironment /2nd hit
Reactants-Normal cell
Product/s-Tumor cell

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