The NFKB-P53 antagonism as part of a rheostat network: practical implication in solving the leukemia relapse principle

Cancer is a complex process that evolves through diverse, intricate mechanisms into a disease where a given cell type loses a certain part of its inherent properties, and gains the capacity to enter tissue niches that it does not belong to. Mutation profiles alone cannot explain why genetically similar clones diverge into distinct clinical trajectories, whereas transcriptional programs often capture these functional differences more directly. Commonly cancer may begin with few molecular changes that bestow to a clone of cells the capacity for growth under conditions that are profoundly incompatible with tissue operation. While inflammation does also entail both immune and non-immune cells entering a functional mode that disrupts tissue operation, the key difference of inflammation with cancer is that cancer changes the cellular identity to the extent that the cell does not identify itself as part of its native tissue anymore, and this abnormality occurs in at least one clone that has reached a cell population size which exceeds a critical threshold to the extent that the clone interferes with vital tissue operation and gains the capacity to grow in organs where it does not belong. In conclusion, although inflammation can cause tissue damage that under certain conditions exceeds the damage that a given cancer causes, what distinguishes cancer is the drastic alteration of typical features that identify a given cell type, even if this alteration may revert to some extent. The reaction of the host organism to cancer is a cataclysmic chain of events that entail destruction of great numbers of cancer cells, by diverse mechanisms. Cancer treatment also aims to kill enough cancer cells to make the task of the host organism easier, in returning to normal operation, and ideally into the mode of homeostasis, within the thresholds that permit optimum function for the entire organism and the corresponding flow equilibrium of biochemical reactions. We propose a simple rheostat metric to summarize NFKB–P53 antagonism and to prioritize samples for follow‑up and validation.