Preclinical studies reveal that LSD1 inhibition results in tumor growth arrest in lung adenocarcinoma independently of driver mutations.

ABSTRACT: Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Despite the development of novel targeted and immune therapies, the 5-year survival rate is still only 21%, indicating the need for more efficient treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser that modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option for treating LUAD. The reversible LSD1 inhibitor HCI-2509 significantly reduced cell growth with an IC₅₀ of 0.3-5 μmin vitro, which was linked to an enhancement of histone 3 lysine methylation. Most importantly, growth arrest, as we

SUBMITTER: Macheleidt IF 

PROVIDER: S-EPMC6210049 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature