The role of p38 MAP kinase in cancer cell apoptosis

Abstract

Background. Cellular behaviour in response to many extracellular stimuli is mediated through MAP kinase signalling pathways. p38 MAP kinase that is represented in mammals by four isoforms ( p38α, p38β, p38γ and p38δ) is one of the four main subgroups of MAP kinases. Recent studies show that p38 activation is necessary for cancer cell death initiated by variety of anti-cancer agents. This finding connected cancer therapies previously considered to be mechanistically unrelated and raised the possibility of developing anti-cancer agents that lack the side effects caused by events upstream of p38 MAPK. Many of the details of p38 induced apoptosis still need to be elucidated. Since most of the past studies rely only on the cell culture models, all the results have to be verified using in vivo models. Also very little is known about the role of p38 mediated apoptosis on non-neoplastic cells in response to anti-cancer agents.

Conclusion. Although p38 activation of cancer cell apoptosis is a very complex process, recent studies indicate a good starting point for new strategies that would increase the efficiency and decrease the toxicity of proven therapies.