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Morphologic-Molecular Transformation of Oncogene Addicted Non-Small Cell Lung Cancer

Fiorella Calabrese1, Federica Pezzuto1, Francesca Lunardi1

  • 1Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padova, 35128 Padova, Italy.

International Journal of Molecular Sciences
|April 23, 2022
PubMed

Insights

Non-small cell lung cancer patients can develop resistance to targeted therapies like tyrosine kinase inhibitors (TKIs). Histological transformations, such as to small cell lung carcinoma, are key resistance mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Non-small cell lung cancer (NSCLC) often harbors oncogenic driver mutations.
  • Targeted therapies, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), have improved patient outcomes.
  • Acquired resistance to TKIs remains a significant clinical challenge.

Purpose of the Study:

  • To review tyrosine kinase inhibitors (TKIs) and their biological activities in EGFR-mutated NSCLC.
  • To discuss histological and molecular transformations as mechanisms of TKI resistance.
  • To provide an updated review of reported cases and discuss future research directions.

Main Methods:

  • Review of current literature on TKI agents and their mechanisms of action.
  • Analysis of documented cases of histological and molecular transformations in NSCLC.
  • Discussion of liquid biopsy applications and future research avenues.

Main Results:

  • Transformations to other histotypes (small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, sarcomatoid carcinoma) are recognized resistance mechanisms.
  • These transformations represent a significant challenge in the management of EGFR-mutated NSCLC.
  • An up-to-date review of published cases highlights the prevalence and impact of these transformations.

Conclusions:

  • Histological and molecular transformations are critical mechanisms of acquired resistance to targeted therapies in NSCLC.
  • Understanding these transformations is essential for optimizing diagnosis, management, and patient care.
  • Liquid biopsy offers promising avenues for early detection and monitoring of resistance.
Keywords:
non-small cell lung canceroncogene addictedsmall cell lung cancer

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