Fine Graining in the Cancer context

Coarse graining of cellular macrostates can be done at the macroscale. For e.g. if there are cellular macrostates A--->B<=>C---->D, it can be coarse grained to A--->B/C--->D, where A is a group of cancer cells that divide but to a limited extent forming a  pre-cancerous lesion (B) or a benign tumor(C). B and C are interchangeable. When either B or C overcomes the inhibitory signaling of the tumor microenvironment they get converted to a malignant/metastasizing state (D). If  A and D are considered analogous to a  binary switch 0/1 , then the transition between the normal cell and a tumorigenic cell can be considered as :off/on; A/B;0/1 states which can be coarse grained with a single intermediary state B/C.

However each cellular macrostate can consist of  temporally regulated dynamic signal transduction networks. A--->B transition can be considered a series of microstate transitions such as a--->a1--->a2---->a3........b.
Each microstate is a certain configuration of signal transduction networks. For eg a cell with an activating mutation in an oncogene will possess aberrant signaling. A=Normal cell. Oncogenic mutation during replication occurs. Inorder to manifest oncogenic activity the oncogenic protein will initiate and proceed with uncontrolled signaling.
 Microstate a1 is the initiating signaling activity by a single molecule of oncogenic protein. A critical pool of molecules of the oncogenic protein build up slowly say  states a2,a3,a4 , following which sustained signaling by the pool of oncogenic molecules occurs. At various time points the cellular lysates will show different concentrations of the oncogenic proteins.

So a drug candidate can do the following
1) targets oncogenic mutation in state A
2)prevents build up of critical pool of oncogenic protein to 'x' no. of molecules i.e prevents transition from state A
3)prevents signaling by the built pools of oncogenic protein with 'x' no. of molecules i.e.prevents signaling in state B

Depending on the model of tumorigenesis developed by fine graining the best drug candidate can be developed.


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