GSE211272
ATR inhibition using gartisertib enhances cell death and synergises with temozolomide and radiation in patient-derived glioblastoma cell lines
Glioblastoma is an aggressive and highly invasive disease that often resists treatment. Tumour cells can restrict the DNA-damaging effects of temozolomide (TMZ) and radiation therapy (RT) using the DNA damage response (DDR) mechanism which activates cell cycle arrest and DNA repair pathways. Ataxia-telangiectasia and Rad3-Related protein (ATR) plays a pivotal role in the recognition of DNA damage induced by chemotherapy and radiation and downstream activation of DDR pathways. Furthermore, a growing body of evidence indicates DNA damage and inhibition of ATR can stimulate a proinflammatory response that activates innate immunity against tumour cells. Here, we investigated the change of gene expression of treated glioblastoma cell lines from TMZ+RT and ATR inhibition (using gartisertib (M4344)) combined with TMZ+RT. Overall design: We treated glioblastoma cell lines (n=12) with DMSO control, TMZ+RT and M4344+TMZ+RT (2x biological replicates) and cells were grown for 4 days before RNA was extracted for downstream gene expression analysis.