Histologic transformation to lung squamous cell carcinoma (LUSC) is an underrecognized mechanism of resistance in epidermal growth factor receptor ( EGFR )–mutant lung adenocarcinoma (LUAD).

The gap

Consensus across the literature

Supporting evidence — 3 representative gaps

• Histological transformation in lung cancer: a single-arm meta-analysis and systematic review (2026) · doi

  Abstract Background Histological transformation represents an important mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant lung cancer; however, its incidence, timing, and post-transformation outcomes remain incompletely characterized.

  Keywords: transformation egfr abstract background histological represents important mechanism acquired resistance epidermal growth factor receptor tyrosine
• Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR (2010) · doi

  BACKGROUND: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.

  Keywords: egfr background small cell lung cancer sensitive mutations epidermal growth factor receptor highly responsive tyrosine
• Clinicogenomic analysis of <i>EGFR</i> -mutant lung tumors identifies Rb pathway inactivation as a hallmark of squamous transformation (2026) · doi

  Histologic transformation to lung squamous cell carcinoma (LUSC) is an underrecognized mechanism of resistance in epidermal growth factor receptor ( EGFR )–mutant lung adenocarcinoma (LUAD).

  Keywords: lung histologic transformation squamous cell carcinoma lusc underrecognized mechanism resistance epidermal growth factor receptor egfr