Unveiling the role of MGMT and DAPK hypermethylation in response to anti-EGFR agents: Molecular insights for advancing HNSCC treatment

Head Neck. 2024 Mar;46(3):461-472. doi: 10.1002/hed.27602. Epub 2023 Dec 14.

Abstract

Background: Epidermal growth factor receptor (EGFR) is frequently activated in head and neck squamous cell carcinoma (HNSCC) and serves as a valuable target for therapy. Despite the availability of the EGFR inhibitors Cetuximab, Afatinib, and Allitinib, there are limited predictive markers for their response. Understanding molecular aberrations in HNSCC could facilitate the identification of new strategies for patient clinical and biological classification, offering novel therapeutic avenues.

Methods: We assessed CCNA1, DCC, MGMT, CDKN2A/p16, and DAPK methylation status in HNSCC cell lines and their association with anti-EGFR treatment response.

Results: MGMT methylation status displayed high sensitivity and specificity in distinguishing sensitive and resistant HNSCC cell lines to Afatinib (AUC = 0.955) and Allitinib (AUC = 0.935). Moreover, DAPK methylation status predicted response to Allitinib with high accuracy (AUC = 0.852), indicating their putative predictive biomarker roles.

Conclusion: These findings hold promise for the development of more personalized and effective treatment approaches for HNSCC patients.

Keywords: HNSCC; anti-EGFR; biomarkers; precision medicine; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides*
  • Afatinib
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Cell Line, Tumor
  • Cetuximab / pharmacology
  • Cetuximab / therapeutic use
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / therapeutic use
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / therapeutic use
  • ErbB Receptors / metabolism
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Quinazolines*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Tumor Suppressor Proteins

Substances

  • AST 1306
  • Afatinib
  • Cetuximab
  • ErbB Receptors
  • EGFR protein, human
  • MGMT protein, human
  • DNA Modification Methylases
  • Tumor Suppressor Proteins
  • DNA Repair Enzymes
  • Acrylamides
  • Quinazolines