====== Differentiation therapy ======

Differentiation [[therapy]] is a method to treat advanced cancers in which malignant cells are encouraged to differentiate into more mature forms using pharmacological agents. The basis of the therapy stems from the tendency of malignant tumor cells to assume a less specialized, stem cell-like dedifferentiated state.
----
[[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 [[proteomic analysis]] 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.)).