Chromosomal Instability Is Associated with cGAS-STING Activation in EGFR-TKI Refractory Non-Small-Cell Lung Cancer.

ABSTRACT: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard therapies for EGFR-mutated non-small-cell lung cancer (NSCLC); however, their efficacy is inconsistent. Secondary mutations in the EGFR or other genes that lead to resistance have been identified, but resistance mechanisms have not been fully identified. Chromosomal instability (CIN) is a hallmark of cancer and results in genetic diversity. In this study, we demonstrated by transcriptomic analysis that CIN activates the cGAS-STING signaling pathway, which leads to EGFR-TKI refractoriness in a subset of EGFR-mutated NSCLC patients. Furthermore, EGFR-mutated H1975dnMCAK cells, which frequently underwent chromosomal mis-segregation, demonstrated refractoriness to the EGFR-TKI osime

SUBMITTER: Yonesaka K 

PROVIDER: S-EPMC11941500 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature