Activating a tumor suppressor/inhibiting an oncogene within a tumor by a drug may alter tumor cellular state. Tumor cells may adapt and give survival cues to the tumor microenvironment. So drug has to target signaling by tumor microenvironment to tumor cells. So not one drug but two, targeting tumor cell +tumor microenvironment.
Cellular States in Cancer: Visualization-Oscillating pendulum
Cellular states preceding and following tumorigenesis are like- an oscillating pendulum that overshoots mean position once (equivalent to cellular state i.e benign tumor after primary mutational hit-State A). The pendulum tries to come back to mean balance position (equivalent to restoring homeostasis in cell after primary mutational hit). Due to loss of elasticity of pendulum string (equivalent to secondary hit due to tumor microenvironment interactions) status quo of extreme position maintained, (which is equivalent to malignant tumor-State B ).
the analogy is limited. water is not proliferating like tumor cells. If one just targets the microenvironment the tumor cells will keep on sending survival cues to adapt-Darwinian evolution -survival of the fittest. One has to target this adapting process within a cell and outside it both ways. a better analogy would be a seed and soil- a seed can accumulate mutation to germinate in a non proliferative soil eg cacti grow in the desert. so target the seed and the soil. adaptation is natures law. Thank you for the thoughtful response Dr. Tez.
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A tumor cell has already undergone a phase transition from a normal to a tumor cell due to a mutation-first mutational hit-State A .
An ice cube/normal cell can melt to water/pre cancerous lesion (State A) water turns to gas/cancer (State B). Lower the temperature gas can turn to water to ice, but the temperature is the environment while the mutation is within the tumor. So cell continues to proliferate and adapt. Water has no inherent change other than that caused by the environment/temperature.Malignant tumor due to tumor cell microenvironment interplay. Phase transition equivalent to normal cell environment interplay. Thank You.
Yes Agree with the above statement. It is the emergent interactions of mutated proteins in the water compared to the water per se that is promoting tumorigenesis.
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