Transformation to Neuroendocrine Phenotype in Non-Small-Cell Lung Carcinoma: A Literature Review

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.