Regulating autophagy is a treatment strategy for high-level gliomas in children

Autophagy is a highly conservative biological metabolic process that is raised in pHGG to promote tumor progression and escape tumor cell deathThere is a significant correlation between autophagy and many key signaling pathways, many of which are dysfunctional in pHGG- From the article(Ref: Howarth A, et alBrain Pathol2019 Apr 23doi: 10.1111/bpa.12729After decades of research, the treatment of high-level glioma (pHGG) in children is still poor and clinical prognosis is poorAutophagy is a highly conservative biological metabolic process that is raised in pHGG to promote tumor progression and escape tumor cell deathThere is a significant correlation between autophagy and many key signaling pathways, many of which are dysfunctional in pHGGAlison Howarth of the Brain Tumour Research Centre at the University of Portsmouth, UK, and others reviewed advances in research on the pHGG autophagy-related signaling pathway and its therapeutic effect as a target, published online in Brain Pathology in April 2019PI3K/AKT/mTOR signaling pathways and PTEN regulation: phosphate inositol-3 kinase (PI3K) signalconductise network spnea is widely distributed, regulating a variety of physiological activities of cells, including proliferation, cell survival and metabolismThe PI3K signal path is negatively regulated by PTENPTEN is an important tumor suppressor that often mutates in cancerPTEN adjusts the PI3K/AKT/mTOR pathway by dephosphateing negative, and the path can be observed in pHGGIn adult high-level gliomas, PTEN often mutates as "inactive" PTEN mutations are rarer in pHGG patients and are often shown as heterogeneity A high proportion of pHGG tumors involve PI3K signaling pathways, so PI3K is an attractive target therapeutic pathway, especially mTOR inhibitors mTOR regulation of autophagy activity: In the upstream of mTOR, AKT promotes mTOR signal conduction through TSC2, thus preventing the formation of TSC1/TSC2 complexes and disabling the RAS homologous (Rheb) inhibition of the brain." DNA damage response response (DNA reaction damage, DDR): mainly involved in the identification and repair of DNA damage Autophagy participates in the regulation of DDR by providing the substance needed for DNA repair Therefore, a more comprehensive understanding of the role of DDR in inducing and regulating autophagy may be the key to improving the sensitivity of pHGG radiation chemotherapy epigenetic regulation and effects on DDR and autophagy in pHGG: The most common mutation in pHGG is a mutation in the core histoneh h1 and H3 caused by amino acid displacement, which can be found in K27 (K27M) and G34 (G34R/V) residues These mutations lead to genomic instability and resistance to treatment from pediatric tumors Studies have shown that DNA damage signals, DDR and autophagy regulation have an association in pHGG growth factor signaling pathways and autophagy in pHGG: expression abnormalities of receptor tyrosine kinases EGFR, PDGFR and VEGF in pHGG, and the occurrence of autophagy induced after RTK inhibition suggest that by regulating these signaling molecules and autophagy activity, there may be potential therapeutic effects on pHGG autophagy regulation on redoning chemotherapy and the clinical application of autophagy regulation in pHGG: autophagy has been shown to regulate chemotherapy in pHGG patients After active multidrug treatment, there was a difference in the expression of autophagy-critical proteins in first-time patients and relapsed patients Drugs for the treatment of pHGG autophagy are mainly mTOR inhibitors: repamycin or repalogogus, including siromos, evirolimus and temsirolimus (Table 1) table 1 Clinical trial data for autophagy treatment.