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Updated: Oct 17, 2025

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[Clinical characteristics of epidermal growth factor receptor-mutated advanced adenocarcinoma transformed into

C Chen1, J A Huang1, C G Wang1

  • 1The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.

Zhonghua Jie He He Hu Xi Za Zhi = Zhonghua Jiehe He Huxi Zazhi = Chinese Journal of Tuberculosis and Respiratory Diseases
|October 14, 2021
PubMed

Insights

Epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma can transform into aggressive small-cell lung cancer, indicating a poor prognosis and a mechanism of drug resistance. Further research is needed to clarify the exact transformation mechanisms.

Area of Science:

  • Oncology
  • Genomics
  • Pathology

Background:

  • Epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is a common subtype of non-small cell lung cancer.
  • Acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is a significant clinical challenge.
  • Transformation to small-cell lung cancer (SCLC) is an emerging mechanism of resistance.

Purpose of the Study:

  • To investigate the clinicopathological and genomic features of EGFR-mutated lung adenocarcinoma that transformed into SCLC.
  • To understand the potential mechanisms driving this transformation and its implications for treatment resistance.

Main Methods:

  • Retrospective analysis of four patients with EGFR-mutated advanced lung adenocarcinoma transformed into SCLC.
  • Evaluation of clinical data, pathological morphology, immunohistochemistry, and comprehensive gene mutation profiling.

Main Results:

  • The study identified heterogeneity in clinical and genomic profiles of these transformed tumors.
  • Commonly observed mutations included RB1, TP53, and PIK3CA.
  • Transformation to SCLC represents an aggressive drug resistance mechanism, though specific pathways remain unclear.
  • Tumor markers like neuron-specific enolase (NSE) showed limited diagnostic value for this transformation.

Conclusions:

  • Transformation of EGFR-mutated lung adenocarcinoma to SCLC is a key factor in EGFR resistance.
  • This transformation is associated with a very poor prognosis.
  • Understanding the genomic landscape and resistance mechanisms is crucial for developing effective therapeutic strategies.

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