Loading
Life sciences · Journal article
Genes · November 6, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy defined by a number of genetic and molecular features, including near-universal TP53 and RB1 inactivation, MYC amplifications, Notch pathway disruption, and hyperactivated PI3K/AKT/mTOR signaling. The subtypes of SCLC, SCLC-A/N/P/I, are primarily based on four transcription regulators (ASCL1, NeuroD1, YAP1, POU). This review provides a concise overview of the molecular landscape of SCLC and then focuses on the subset displaying epidermal growth factor receptor (EGFR) alterations. EGFR-positive SCLC presents either as rare primary (de novo) disease (2.6–19.3%) or as transformed SCLC originating from EGFR-mutant non-small cell lung cancer (NSCLC) in 3–14% of cases following EGFR tyrosine kinase inhibitor (TKI) therapy. In both cases, the tumors harbor EGFR mutations with the most frequent one being exon 19 deletions. A number of pathways have been identified regarding the lineage transformation with the co-occurring TP53 and RB1 loss predominating, while a number of other molecular mechanisms have been explored, including activation of epithelial-to-mesenchymal transition factors (ZEB1, SLUG), MDM4 or BCL2L2/NFKBIA co-amplifications, and newly postulated genetic variants such as FBN1 and PALLD, alongside emergent surface expression of DLL3, B7-H3, and PTK7. Once SCLC transformation occurs, tumors tend to drop EGFR dependence and display profound resistance to EGFR-TKIs, necessitating a shift to standard platinum–etoposide chemotherapy, with or without immunotherapy. The value of EGFR-TKIs has been explored, as an add-on treatment, in several cases and its efficacy has not so far provided satisfactory outcomes. An update of the literature, within this particular field, is being provided along with the value for routine serial re-biopsy (tissue or liquid) upon disease progression, especially when EGFR-TKIs have been used. Early identification of neuroendocrine transformation can prevent futile EGFR-TKI monotherapy, capture mixed histologies, and recognize potential re-transformation back to adenocarcinoma.