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Hepatocyte Growth Factor Reduces Susceptibility to Irreversible EGFR Inhibitors in EGFR-T790M Mutant Lung Cancer

Strategic Insights

— 1 min read

Scientists at Kanazawa University's Cancer Research Institute have discovered a novel mechanism of resistance to irreversible epidermal growth factor receptor (EGFR) inhibitors in lung cancer patients. The study, published in Clinical Cancer Research, found that hepatocyte growth factor (HGF) reduces susceptibility to the irreversible EGFR tyrosine kinase inhibitor CL-387,785 in lung cancer cells harboring both L858R activating mutation and T790M secondary mutation in EGFR.

In their research, T. Yamada and colleagues investigated the effects of HGF on the sensitivity of lung cancer cells to CL-387,785. They found that HGF reduced susceptibility to the inhibitor and that this effect was mediated by the MET/phosphoinositide 3-kinase/Akt signaling pathway, independent of EGFR, ErbB2, ErbB3, and ErbB4. The study's findings suggest that HGF-mediated signaling plays a role in de novo and acquired resistance to irreversible EGFR-TKIs in lung cancer.

Key Takeaways:

  • The study identified a novel mechanism of resistance to irreversible EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer cells harboring T790M mutation in EGFR.
  • Hepatocyte growth factor (HGF) reduces susceptibility to irreversible EGFR inhibitors, such as CL-387,785, in lung cancer cells.
  • The HGF-induced hyposensitivity is mediated by the MET/phosphoinositide 3-kinase/Akt signaling pathway, independent of EGFR, ErbB2, ErbB3, and ErbB4.
  • Coculture with HGF-producing lung fibroblasts induces hyposensitivity of lung cancer cells to CL-387,785.

Statistics:

  • 174-83. (2010.): The reference number of the study published in Clinical Cancer Research.
  • 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.: The publisher of the journal Clinical Cancer Research.
  • 2010: The year the study was published.

Sources:

  • Yamada, T. et al. (2010). Hepatocyte growth factor reduces susceptibility to an irreversible epidermal growth factor receptor inhibitor in EGFR-T790M mutant lung cancer. Clinical Cancer Research, 16(1), 174-83.
  • American Association Cancer Research
  • NewsRx.com
  • Cancer Weekly editors via staff reports (2010)

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