Synergistic Enhancement of Osimertinib Efficacy in Non-Small Cell Lung Cancer

Strategic Insights -

Researchers from M.S. Ramaiah University of Applied Sciences have discovered a novel approach to overcoming resistance to osimertinib, a third-generation epidermal growth factor receptor inhibitor, in non-small cell lung cancer (NSCLC). By combining osimertinib with epigallocatechin-3-gallate (EGCG), a green tea polyphenol, they found that the combination therapy significantly enhanced osimertinib's efficacy in NSCLC cells.

Key Takeaways:

  • The study demonstrated that EGCG effectively targets the Hippo signaling pathway to overcome osimertinib resistance in NSCLC cells.
  • The combination treatment of osimertinib and EGCG showed strong synergy, with a combination index (CI) value indicating synergism across a range from IC50 to IC95.
  • Mechanistically, co-treatment suppressed the overexpression of the YAP/TEAD/CTGF axis, restoring Hippo pathway activity and reversing osimertinib resistance.
  • The inclusion of EGCG in combinatorial therapies holds promise as a novel approach to combat therapeutic resistance and improve outcomes for patients with EGFR-mutated NSCLC.
  • Ashwini Somayaji, the lead researcher, suggested that this study provides evidence that EGCG effectively targets the Hippo signaling pathway to overcome osimertinib resistance in NSCLC.
  • The study's findings were published in the Advanced Pharmaceutical Bulletin, a peer-reviewed journal published by Tabriz University of Medical Sciences.

Statistics:

  • IC50 values for osimertinib in parental H460 cells were 2.74±0.2M, while in osimertinib-resistant (OR) clones, the values were 25.12-28.48M.
  • EGCG treatment reduced cell viability in a concentration-dependent manner, with IC50 values of 102.54±0.23mM for H460 cells and 225.79-237.36M for OR clones.
  • The combination treatment of osimertinib and EGCG showed strong synergy at a 1:2 molar ratio, with CI values indicating synergism across a range from IC50 to IC95.

Sources:

  • NewsRx. Data on Non-Small Cell Lung Cancer Reported by Researchers at M.S. Ramaiah University of Applied Sciences (Synergistic Enhancement of Osimertinib Efficacy in Non-small Cell Lung Cancer Cells Through Epigallocatechin-3-Gallate: Mechanistic ...). Cancer Weekly. September 16, 2025; p 833.
  • Synergistic Enhancement of Osimertinib Efficacy in Non-small Cell Lung Cancer Cells Through Epigallocatechin-3-Gallate: Mechanistic Insights Into YAP/TEAD/CTGF Axis Inhibition. Advanced Pharmaceutical Bulletin, 2025,15(2):428-439. (Advanced Pharmaceutical Bulletin - https://apb.tbzmed.ac.ir/).