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Transformation to Neuroendocrine Phenotype in Non-Small-Cell Lung Carcinoma: A Literature Review
Irene Hernández de Córdoba1, Xabier Mielgo-Rubio2, Paloma Cejas3
1Department of Medical Oncology, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, 28702 Madrid, Spain.
Abstract:
Neuroendocrine transformation in non-small-cell lung cancer (NSCLC) is an uncommon but clinically significant resistance mechanism to targeted therapy, immunotherapy, and chemotherapy. This phenomenon, primarily observed in adenocarcinoma (ADC) with EGFR mutations under tyrosine kinase inhibitor (TKI) treatment, leads to histological transformation into small-cell lung cancer (SCLC), commonly associated with an aggressive clinical course and poor prognosis. Standard platinum-etoposide chemotherapy provides only transient disease control, highlighting the urgent need for improved therapeutic strategies. Early identification of transformation through biopsy, liquid biopsy, or biomarkers like neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (pro-GRP) may allow for early intervention. As targeted therapies continue to develop, understanding the molecular drivers of neuroendocrine transformation is crucial for optimizing treatment. Further research into novel treatment approaches, including combination therapies with TKIs, chemotherapy, immunotherapy, and epigenetic modulators, is required to improve outcomes for these patients.
Insights
Neuroendocrine transformation in non-small-cell lung cancer (NSCLC) is a resistance mechanism to cancer treatments. Early identification and novel therapies are crucial for improving outcomes in these aggressive cases.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Neuroendocrine transformation is a rare but significant resistance mechanism in non-small-cell lung cancer (NSCLC).
- This transformation, particularly in EGFR-mutated adenocarcinoma (ADC) under tyrosine kinase inhibitor (TKI) treatment, leads to small-cell lung cancer (SCLC) with aggressive behavior and poor prognosis.
Purpose of the Study:
- To highlight the clinical significance of neuroendocrine transformation in NSCLC.
- To emphasize the need for improved therapeutic strategies and early detection methods for this phenomenon.
Main Methods:
- Review of clinical observations and existing literature on neuroendocrine transformation in NSCLC.
- Discussion of diagnostic approaches including biopsy, liquid biopsy, and biomarker analysis (NSE, pro-GRP).
Main Results:
- Neuroendocrine transformation confers resistance to targeted therapy, immunotherapy, and chemotherapy.
- Standard platinum-etoposide chemotherapy offers only temporary disease control.
Conclusions:
- Early identification of neuroendocrine transformation via biopsy, liquid biopsy, or biomarkers is critical for timely intervention.
- Further research into molecular drivers and novel combination therapies (TKIs, chemotherapy, immunotherapy, epigenetic modulators) is essential to improve patient outcomes.
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