Publication: NSCLC PDX Models with EGFR Exon 20 Insertions Developed

Yang M et al. NSCLC harboring EGFR exon-20 insertions after the regulatory C-helix of kinase domain responds poorly to known EGFR inhibitors. Int J Cancer 2016;139(1): 171-176.

Activating EGFR mutations are oncogenic drivers in a significant proportion of NSCLC cases. Patients with classical EGFR mutations usually respond well to tyrosine kinase inhibitors (TKI). However, the efficacy of EGFR TKIs on NSCLC cases harboring non-canonical mutations (e.g. exon 20 insertions) is less clear.

Anecdotal clinical observations suggest that NSCLC with exon 20 insertions respond poorly to EGFR TKIs. The lack of preclinical models with these clinically relevant genotypes has hindered the testing of this hypothesis, and the development of new agents against these specific mutations.

This publication details the generation of two NSCLC patient-derived xenograft (PDX) models, harboring different exon 20 insertions, and their varying response to a range of EGFR TKIs e.g. erlotinib, gefitinib, afatinib, osimertinib, rociletinib, as well as cetuximab. The paper also details the generation and testing of PDX-derived cell lines, useful for in vitro studies.

Download This Publication To Understand:

  • That NSCLC PDX models harboring EGFR exon 20 insertions are largely resistant to EGFR TKIs and cetuximab in vivo, consistent with anecdotal clinical reports
  • How in vivo response to EGFR TKIs varies for different exon 20 insertions, revealing that the exact nature of the insertion may guide clinical drug choice
  • That exon 20 insertion NSCLC PDX models can be utilized to facilitate the discovery of new therapies targeting these clinically relevant mutations

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