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The following is a summary of “Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer,” published in the February 2025 issue of Journal of Hematology & Oncology by Yoo et al.
Small cell lung cancer (SCLC) responds to etoposide and platinum (EP) chemotherapy but relapses with resistant tumors. Immunotherapy helps few, and resistance mechanisms remain unclear.
Researchers conducted a retrospective study to investigate resistance mechanisms in SCLC using recent genomic advances.
They constructed a regulatory network for SCLC, identifying granulin precursor (GRN) as a hub gene for EP response, and analyzed its expression in patient samples and single-cell RNA-seq data.
The results showed that patients with GRN-low had better survival with chemotherapy, while patients with GRN-high were resistant. GRN overexpression conferred EP resistance and suppressed neuroendocrine features. GRN and its genes were linked to cancer cell immunogenicity, with high expression in tumor-associated macrophages. GRN-low tumors benefited from chemo-immunotherapy, while GRN-high tumors did not. GRN-high tumors, linked to non-neuroendocrine (non-NE) subtypes, had increased macrophage infiltration, contributing to immunotherapy resistance.
Investigators identified GRN as a chemo-resistance regulator and immunotherapy biomarker in SCLC. Targeted therapies improved GRN-low outcomes, while new strategies were needed for patients with GRN-high.
Source jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01667-5
