Targeting LSD1: A Promising Therapeutic Strategy in Cancer Treatment

Lysine specific demethylase 1 (LSD1) is an enzyme that modifies histones and is implicated in the regulation of gene expression, playing a significant role in various cancers. The study presents the effects of GSK2879552, a novel and irreversible LSD1 inhibitor, on acute myeloid leukemia (AML) and small cell lung cancer (SCLC).

GSK2879552 was identified as a potent and selective mechanism-based inhibitor of LSD1. It was found to be particularly effective against AML and SCLC cells, which exhibit a unique dependence on LSD1. The treatment induced local changes in histone marks associated with gene expression increases and enhanced the surface expression of differentiation markers in AML cells.

In a comprehensive study, GSK2879552 demonstrated significant anti-proliferative effects on 19 of 25 AML cell lines and inhibited the colony-forming ability of AML blasts derived from primary patient samples. In vivo, the compound drastically reduced the presence of GFP+ cells in the bone marrow of mice with AML, extending their survival.

Similarly, SCLC cell lines showed growth inhibition with GSK2879552 treatment, and the efficacy was confirmed in patient-derived primary SCLC samples, indicating that the inhibitor's effects are not limited to cell lines but are also relevant in human cancer.

The findings support the potential of LSD1 inhibition as a therapeutic strategy for both AML and SCLC. Encouraging results from these preclinical studies led to the initiation of a Phase I clinical trial with GSK2879552 in March 2014. All research was conducted following ethical guidelines and policies for the care and treatment of laboratory animals.