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Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors

Yi Shao1, Dian-Sheng Zhong2

  • 1Department of Medical Oncology, Tianjin Medical University General Hospital, No154 Anshan Road, Heping Dist, Tianjin, 300052, China.

International Journal of Clinical Oncology
|November 8, 2017
PubMed

Insights

Histological transformation is a rare cause of resistance to tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer. Further research is needed to understand its mechanisms and guide new treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Non-small-cell lung cancer (NSCLC) patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs).
  • Acquired resistance to TKIs typically develops within 8-16 months.
  • Mechanisms of resistance include T790M mutation, c-Met amplification, and epithelial-mesenchymal transition, but histological transformation is rare.

Purpose of the Study:

  • To explore the patterns and mechanisms of histological transformation in NSCLC following TKI resistance.
  • To review existing literature on rare resistance mechanisms in NSCLC.

Main Methods:

  • A comprehensive literature search was conducted using PubMed, EMBASE, Google Scholar, and Medical Matrix.
  • Included case reports, case series, and clinical/basic research articles.
  • Sixty-one articles were reviewed.

Main Results:

  • Histological transformation to small-cell lung cancer, squamous cell carcinoma, large-cell neuroendocrine carcinoma, and sarcoma has been reported after TKI resistance.
  • Clinical courses varied significantly among transformation types.
  • Mechanisms remain largely unelucidated, potentially involving cancer stem cells, genetic alterations, or tumor heterogeneity.

Conclusions:

  • Histological transformation is a rare but significant mechanism of TKI resistance in NSCLC.
  • The diverse clinical presentations necessitate tailored treatment strategies.
  • Second biopsies upon TKI resistance are recommended for accurate diagnosis, treatment guidance, and prognosis.
Keywords:
Acquired resistanceEpidermal growth factor receptorHistological transformationLung carcinomaTyrosine kinase inhibitor

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