TP53 and neoplasm: We suggest that mutant p53 may function as a key player in the modulation of the tumor–stroma crosstalk both at the initiation as well as the progression of the tumor–stroma vicious cycle, during which mutant p53 facilitates the adaptation (“re-education”) of the stroma cells to tumorigenic-promoting cells in the stromal compartment, as well as causing a modulation of the signals arriving from the stromal cells in a way that benefits the tumor cells.