Differentiation of malignant to benign cells

Jacob & Monod, and Pitot & Heidelberger have suggested that stable misbehavior of genetic control systems might underlie cancer. Since their papers, considerable insight into the behavior of complex gene control nets has accumulated, and suggests the following. The genome is to be considered a complex dynamic system with a finite number of distinct stable modes of behavior, each of which corresponds to a distinct cell type. Differentiation involves passing among these stable modes of behavior. Regardless of whether higher cells have evolved precise control mechanisms to pass among the stable dynamic modes of behavior, cells are continuously oerturbed by biochemical fluctuations which also cause the system to pass among its stable modes of behavior. Such fluctuations are likely to underlie aberrant differentiation. Global features of "aberrant differentiation" in model genetic nets predicts global features of transdetermination experiments. Models and experiments jointly suggest that the normal organism utilizes only a subset of the cell types of which its genome is capable without mutation, thus epigenetic cancer is at least possible. Pathways of differentiation among these normally unutilized cell types exist, and cancer cells might be induced to differentiate along them. Mutation may alter only the pathways of differentiation among cell types, or the cell types themselves. The former case is similar to epigenetic cancer, for cells would follow mutated pathways to reach normally nonutilized cell types of which the non-mutated genome was capable. Such neoplasia might also be induced to differentiate to non-malignant behavior. Even if all cell types are altered by a somatic mutation, not all of them are necessarily malignant-controlled differentiation to such non-harmful cell types might be possible.

Where available, experimental evidence supporting these predictions is examined.