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Histological transformation in lung cancer: Mechanisms, clinical characteristics, and therapeutic approaches

  • 0Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Biochimica Et Biophysica Acta. Reviews on Cancer +

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August 10, 2025

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August 10, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Lung cancer can transform from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC). Understanding this transformation, driven by genetic changes and an immunosuppressive tumor microenvironment, is key to developing new treatments.

Area Of Science

  • Oncology
  • Cancer Biology
  • Molecular Pathology

Background

  • Lung cancer is a leading global cause of mortality.
  • Histological plasticity, particularly the transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), is a significant challenge in treatment resistance.
  • The molecular drivers and therapeutic strategies for SCLC transformation are not well understood.

Purpose Of The Study

  • To review the mechanisms, molecular features, and treatment landscape of histological transformation in lung cancer, with a focus on EGFR-mutant NSCLC.
  • To provide a comprehensive framework for understanding SCLC transformation.
  • To highlight the clinical implications for early detection and targeted therapies.

Main Methods

  • Literature review and analysis of existing studies on lung cancer histological transformation.
  • Examination of molecular alterations, including genetic mutations and epigenetic changes.
  • Assessment of the tumor immune microenvironment during transformation.
  • Review of current and emerging therapeutic strategies.

Main Results

  • Co-inactivation of RB1 and TP53 is a key molecular hallmark of transformed SCLC, facilitating lineage plasticity.
  • The tumor immune microenvironment shifts towards an immunosuppressive state during transformation.
  • Emerging therapies targeting DLL3 and AURKA demonstrate early promise in clinical trials.

Conclusions

  • Histological transformation in lung cancer, particularly NSCLC to SCLC, is a complex process driven by specific molecular alterations.
  • Routine re-biopsies are crucial for early detection of transformation.
  • Biomarker-guided therapies and combination treatments are essential for effectively managing transformed SCLC.

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