p38_mitogen-activated_protein_kinases [Neurosurgery Wiki]

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p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases ([[MAPK]]s) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy.
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[[Differentiation therapy]] has been proposed as an alternative for [[glioblastoma treatment]], with the aim of bringing cancer cells into a post-mitotic/differentiated state, ultimately limiting [[tumor growth]]. As an integral component of cancer development and regulation of differentiation processes, [[kinase]]s are potential targets of differentiation therapies. 

Lane et al. in a study describe how the [[screening]] of a panel of [[kinase inhibitor]]s (KIs) identified PDGF-Rα/β inhibitor [[CP-673451]] as a potential differentiation agent in [[glioblastoma]]. They show that targeting PDGF-Rα/β with [[CP-673451]] in vitro triggers the [[outgrowth]] of neurite-like processes in [[glioblastoma cell line]]s and [[glioblastoma stem cell]]s (GSCs), suggesting differentiation into neural-like cells while reducing [[proliferation]] and [[invasion]] in 3D [[hyaluronic acid hydrogel]]s. In addition, they report that treatment with CP-673451 improves the anti-tumor effects of [[temozolomide]] [[in vivo]] using a subcutaneous [[xenograft]] [[mouse model]]. RNA sequencing and follow-up [[proteomics]] revealed that [[upregulation]] of phosphatase [[DUSP1]] and consecutive [[downregulation]] of phosphorylated-[[p38 mitogen-activated protein kinases]] can underlie the pro-differentiation effect of CP-673451 on Glioblastoma cells. Overall, the present study identifies a potential novel therapeutic option that could benefit Glioblastoma patients in the future, through differentiation of residual GSCs post-surgery, with the aim to limit [[glioblastoma recurrence]] and improve [[quality of life]]
((Lane R, Cilibrasi C, Chen J, Shah K, Messuti E, Mazarakis NK, Stebbing J, Critchley G, Song E, Simon T, Giamas G. PDGF-R inhibition induces glioblastoma cell differentiation via DUSP1/p38MAPK signaling. Oncogene. 2022 Apr 7. doi: 10.1038/s41388-022-02294-x. Epub ahead of print. PMID: 35393545.)).