P38 MAPK and Radiotherapy: Foes or Friends?

Simple Summary p38 MAPKs comprise a family of key proteins that regulate the stress response of human cells, controlling relevant biological phenomena such as the cell cycle. As a result, their role in the cellular response to ionizing radiation and radiotherapy is crucial. In this review, we provide in-depth insights into what is known about the whole protein family's role in response to radiation and the implications for radiotherapy. Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in key processes triggered by IR-mediated genotoxic insult, such as the cell cycle, apoptosis or senescence. However, we do not yet have a definitive clue about the role of p38 MAPK in terms of radioresistance/sensitivity and its potential use to improve current radiotherapy. In this review, we summarize the current knowledge on this family of MAPKs in response to IR as well as in different aspects related to radiotherapy, such as their role in the control of REDOX, fibrosis, and in the radiosensitizing effect of several compounds.