large series of imatinib-treated patients with other types of GIST mutations. Consequently, it is critical to define the exact nature of PDGFR-induced mutant GIST tumors in order to select appropriate therapy particularly because a novel PDGFRA selective kinase inhibitor, crenolanib, is under investigation for treating D842V-induced and other imatinib-resistant GIST tumors. A randomized trial testing the efficacy of crenolanib in patients with GIST tumors bearing the D842V mutation is under recruitment. Olaratumab (LY3012207) is a human IgG1 monoclonal antibody designed to bind to human PDGFRα with high affinity and block PDGF-AA, PDGF-BB, and PDGF-CC ligands from binding to the receptor. Numerous studies using it to treat soft tissue sarcomas including GIST are ongoing. Studies on GIST have focused on inoperable, metastatic, and/or recurrent disease and have tested olagatumab with Doxorubicin versus doxorubicin along. The US FDA granted approval for the use of olaratumab-dcoxorbicin therapy of soft tissue sarcomas under its Accelerated Approval Program based on the results of the phase II trial, (NCT01185964). In addition, the European Medicines Agency granted conditional approval for olaratumab in this indication in November 2016 following a review under the EMA's Accelerated Assessment Program. Nervous system Gain-of-function H3K27M mutations in protein histone H3 lead to inactivation of polycomb repressive complex 2 (PRC2) methyltransferase and result in global hypomethylation of H3K27me3 and transcriptional derepression of potential oncogenes. About 40% of these mutation are associated with gain of function or amplifications mutations in the PDGFRA gene in cases of pediatric diffuse Gliomas of the pons. It appears that the initial histone H3 mutations alone are insufficient but rather require cooperating secondary mutations such as PDGFRA-activating mutations or PDGFRA'' amplifications to develop this type of brain tumor. In a small non-randomized trial study, imatinib therapy in patients with glioblastoma selected on the basis of having imatinib-inhibitable tyrosine kinases in biopsy tissue caused marginal disease improvement compared to similar treatment of patients with unselected recurrent glioblastoma. This suggests that patient sub-populations with excessive PDGFRA-related or other tyrosine kinase-related over-activity might benefit from imatinib therapy. Several phase I and Phase II clinical glioma/glioblastoma studies have been conducted using imatinib but no decisive follow-up phase III studies have been reported. Interactions PDGFRA has been shown to interact with: CRK, Caveolin 1, Cbl gene, PDGFC, PDGFR-β, PLCG1, and Sodium-hydrogen antiporter 3 regulator 1. Notes See also Platelet-derived growth factor receptor Clonal eosinophilia References Further reading Tyrosine kinase receptors