2605003847
  • Open Access
  • Article

Antitumor Effects of Afatinib on Tumorigenic Potentials in Triple Negative Breast Cancer

  • Deok-Soo Son 1,*,   
  • Tamara J. Martin  1,   
  • Rosa Mistica C. Ignacio 1,   
  • Sydney E. Harville 2,   
  • Eun-Sook Lee 3,   
  • Samuel E. Adunyah 1

Received: 28 Dec 2025 | Revised: 27 Mar 2026 | Accepted: 08 May 2026 | Published: 19 May 2026

Abstract

Triple-negative breast cancer (TNBC), a highly aggressive subtype characterized by frequent relapse, metastasis, and poor prognosis, exhibits elevated epidermal growth factor receptor (EGFR) expression. Our prior research demonstrated that afatinib, a tyrosine kinase inhibitor, effectively suppressed EGFR-mediated downstream, including AKT and ERK, and reduced epithelial-to-mesenchymal transition (EMT) markers in human TNBC cell models. This study was designed to extend afatinib’s efficacy in mitigating tumorigenic potentials in murine TNBC models. We employed cell viability assays, signaling pathway analyses, cytokine profiling, cell cycle-related protein assessments, and diet-induced obese mouse models to elucidate afatinib’s therapeutic benefits. Afatinib exhibited superior inhibition on cell viability in murine TNBC cells compared to erlotinib, gefitinib, and lapatinib. In PY8119 TNBC cells, afatinib inhibited AKT and ERK phosphorylation, downregulated vimentin and N-cadherin expression, and suppressed cell migration and invasion. Additionally, afatinib reduced proinflammatory chemokine levels, disrupted cell cycle progression, and upregulated necrosis-associated proteins. In diet-induced obese mouse models, afatinib significantly reduced tumor burden. Collectively, these findings suggest that afatinib attenuates TNBC tumorigenicity by inhibiting EGFR-mediated downstream signaling and EMT markers, downregulating proinflammatory chemokines, and disrupting cell cycle progression, supporting its potential as a therapeutic agent for TNBC at preclinical evaluation.

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Son, D.-S.; Martin , T. J.; Ignacio, R. M. C.; Harville, S. E.; Lee, E.-S.; Adunyah, S. E. Antitumor Effects of Afatinib on Tumorigenic Potentials in Triple Negative Breast Cancer. Journal of Inflammatory and Infectious Medicine 2026, 2 (1), 4. https://doi.org/10.53941/jiim.2026.100004.
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