Mitogen-Activated Protein Kinase Cascades as Therapeutic Targets in Cancer

Abstract

Mammalian cell growth is regulated by a large number of environmental cues in the form of extracellular signals. These signals stimulate changes in cell metabolism and gene expression, and induce complex cellular responses such as proliferation, differentiation, or death. However, the genetic mutations that accumulate in cancer allow cells to grow with apparent disregard for their environment, so that, even in the absence of appropriate signals, cells continue to proliferate, or they fail to differentiate or die when instructed to do so. In the past, cancer therapeutic agents were developed in the absence of a clear understanding of the mechanisms that regulate cell growth. The agents that were produced were generally developed to target rapidly dividing cells and are, on the whole, extremely toxic and associated with barely tolerable side effects, because they also target healthy dividing cells. A great deal of research has therefore been directed at understanding the molecular mechanisms that regulate cell growth and to determine why cancer cells grow with such apparent disregard for their environment. It was anticipated that this would provide new molecular targets that were associated with only the rapid division associated with cancer cells, but not with the rapid division associated with normal cells. The hope was that agents that blocked the activity of these targets would be specific for cancer cells over normal cells, leading to fewer side effects and, consequently, offering improved treatments for cancer patients.