2. Academic Validation
  3. Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma

Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma

  • Invest New Drugs. 2023 Jun 16. doi: 10.1007/s10637-023-01373-4.
Hanwen Lu 1 2,  Bingchang Zhang 1 3,  Yuanyuan Xie 1 3,  Wenpeng Zhao 1 2,  Wanhong Han 1 3,  Liwei Zhou 1 3,  Zhanxiang Wang 4 5 6 7
Affiliations

Affiliations

  • 1 The Department of Neuroscience, Institute of Neurosurgery, School of Medicine, Xiamen University, Xiamen City, China.
  • 2 Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, Xiamen City, China.
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, Xiamen City, China.
  • 4 The Department of Neuroscience, Institute of Neurosurgery, School of Medicine, Xiamen University, Xiamen City, China. WangZX@xmu.edu.cn.
  • 5 Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, Xiamen City, China. WangZX@xmu.edu.cn.
  • 6 Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, Xiamen City, China. WangZX@xmu.edu.cn.
  • 7 Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen City, China. WangZX@xmu.edu.cn.
PMID: 37322389 DOI: 10.1007/s10637-023-01373-4
Abstract

Glioblastoma (GBM) is a highly lethal neurological tumor that presents significant challenge for clinicians due to its heterogeneity and high mortality rate. Despite extensive research, there is currently no effective drug treatment available for GBM. Research evidence has consistently demonstrated that the epidermal growth factor receptor (EGFR) promotes tumor progression and is associated with poor prognosis in several types of Cancer. In glioma, EGFR abnormal amplification is reported in approximately 40% of GBM patients, with overexpression observed in 60% of cases, and deletion or mutation in 24% to 67% of patients. In our study, Sitravatinib, a potential EGFR inhibitor, was identified through molecular docking screening based on protein structure. The targeting of EGFR and the tumor inhibitory effect of Sitravatinib on glioma were verified through cellular and in vivo experiments, respectively. Our study also revealed that Sitravatinib effectively inhibited GBM invasive and induced DNA damage and cellular senescence. Furthermore, we observed a novel cell death phenotype induced by Sitravatinib, which differed from previously reported programmed death patterns such as Apoptosis, Pyroptosis, Ferroptosis, and necrosis.

Keywords

Cell death; EGFR; Inhibitor; Molecule docking; Virtual screening.

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