Intrinsic and acquired drug resistance to LSD1 inhibitors in small cell lung cancer occurs through a TEAD4-driven transcriptional state.

ABSTRACT: Small-cell lung cancer (SCLC) is a heterogeneous disease, consisting of intratumoral and intertumoral neuroendocrine (ASCL1 and/or NEUROD1), mesenchymal-like, and YAP-driven transcriptional states. Lysine-specific demethylase 1 (LSD1; also known as KDM1A) inhibitors have recently been progressed to clinical trials in SCLC based on a promising preclinical antitumor activity. A potential clinical limitation of LSD1 inhibitors is the heterogeneous drug responses that have been observed in SCLC cell lines and patient-derived models. Based on these observations, we studied molecular and transcriptional signatures that predict patient response to this class of drug. Employing SCLC patient-derived transcriptional signatures, we define that SCLC cell lines sensitive to LSD1 inhibitors are enriched

SUBMITTER: Yan W 

PROVIDER: S-EPMC8936524 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature