High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis

Cancer Res Commun. 2024 Nov 1;4(11):2919-2932. doi: 10.1158/2767-9764.CRC-24-0136.

Abstract

Mechanistically guided drug repurposing has been made possible by systematically integrating pharmacologic and CRISPR-Cas9 screen data. Our study discovers the biomarker and cell death mechanisms underpinning sensitivity toward AZD5582, an antagonist of the inhibitor of apoptosis family protein. Our findings have important implications for improving future trial design for patients with OSCC using this emerging drug class.

MeSH terms

  • Apoptosis* / drug effects
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Caspase 8* / genetics
  • Caspase 8* / metabolism
  • Cell Line, Tumor
  • Drug Repositioning / methods
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • NF-kappa B* / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • NF-kappa B
  • Caspase 8
  • Tumor Necrosis Factor-alpha
  • CASP8 protein, human
  • TNF protein, human