The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer García Hernández, Laura García Ortega, María Belén Ruiz Alcalá, Gloria Carrillo Delgado, Esmeralda Esperanza Marchal Corrales, Juan Antonio García Chaves, María Ángel Kinases MAPK p38 Cancer Therapy Biomarkers Isoforms This research was funded by MCIN/AEI/10.13039/501100011033/FEDER, grant number RTI2018-101309-B-C22 and by the Chair Doctors Galera-Requena in cancer stem cell research. The mitogen-activated protein kinase (MAPK) family is an important bridge in the transduction of extracellular and intracellular signals in different responses at the cellular level. Within this MAPK family, the p38 kinases can be found altered in various diseases, including cancer, where these kinases play a fundamental role, sometimes with antagonistic mechanisms of action, depending on several factors. In fact, this family has an immense number of functionalities, many of them yet to be discovered in terms of regulation and action in different types of cancer, being directly involved in the response to cancer therapies. To date, three main groups of MAPKs have been identified in mammals: the extracellular signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), and the different isoforms of p38 (alpha, beta, gamma, delta). In this review, we highlight the mechanism of action of these kinases, taking into account their extensive regulation at the cellular level through various modifications and modulations, including a wide variety of microRNAs. We also analyze the importance of the different isoforms expressed in the different tissues and their possible role as biomarkers and molecular targets. In addition, we include the latest preclinical and clinical trials with different p38-related drugs that are ongoing with hopeful expectations in the present/future of developing precision medicine in cancer. 2022-03-08T13:23:36Z 2022-03-08T13:23:36Z 2021-12-29 info:eu-repo/semantics/article García-Hernández, L... [et al.]. The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer. Int. J. Mol. Sci. 2022, 23, 370. [https://doi.org/10.3390/ijms23010370] http://hdl.handle.net/10481/73234 10.3390/ijms23010370 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI