ArticleBioMed research international2022
ZSTK474 Sensitizes Glioblastoma to Temozolomide by Blocking Homologous Recombination Repair.
Article in BioMed research international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 8 citations in OpenAlex.
- Safety and efficacy of depatuxizumab mafodotin monotherapy or in combination with temozolomide in patients with/without EGFR-amplified recurrent glioblastoma: a systematic review.Annals of medicine and surgery (2012) · 2025Article
- Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.Cell genomics · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) is used as the standard chemotherapeutic agent for GBM but with limited success, and treatment failure is mainly due to tumor resistance. One of the leading causes of TMZ resistance is the upregulation of the DNA repair mechanism. Therefore, targeting the DNA damage response (DDR) is proposed to be an effective strategy to sensitize tumor cells to TMZ. In the present study, we demonstrated that the combined use of the PI3K inhibitor ZSTK474 and TMZ showed synergetic anticancer effects on human GBM cells in vitro and in vivo. The combination treatment led to significantly increased cell apoptosis and DNA double strand breaks (DSBs). In addition, a mechanistic study indicated that TMZ enhanced the homologous recombination (HR) repair efficiency in GBM cells, while ZSTK474 impaired HR repair by blocking the phosphorylation of ATM and the expression of BRCA1/2 and Rad51, thereby sensitizing GBM cells to TMZ. Moreover, TMZ activated the PI3K signaling pathway through upregulation of the PI3K catalytic subunits p110
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