Preventing diversification of malignant tumor cells during therapy.

One of the most difficult problems arising during cancer therapy is the emergence of unique tumor cell subpopulations that express altered malignant and therapeutic properties. In model tumor systems cytotoxic therapies that eliminate all but a few tumor cells seem to stimulate cell diversification to yield heterogeneous cell populations with divergent properties. Clinically the use of repeated cycles of cytotoxic therapies followed by intervening recovery periods often results in the eventual emergence of highly resistant and increasingly malignant tumor cells. To circumvent tumor cell diversification during therapeutic recovery periods we suggest that cytostatic agents might be employed. Although cytostatic agents such as differentiation modulators, hormones, growth factors, vitamins, and other natural products are unlikely to be effective therapeutic agents if used alone, they could be used during therapeutic recovery periods to modulate the diversification of surviving tumor cells so that these periods might be characterized by less extensive tumor cell diversification. At the end of recovery periods after the removal of cytostatic agents, surviving tumor cells could be briefly restimulated by growth factors, hormones or mitogens, just prior to initiation of new cycles of therapy using cytotoxic agents.