Dr. Arnaud Augert, Fred Hutchinson Cancer Research Center, published a manuscript in 2019 based on his work in small cell lung carcinoma (SCLC) – a very aggressive cancer with few therapeutic options. Dr. Augert received a 2014 LCRF research grant.
The authors, including Dr. Augert, assessed the anti-tumor properties of ORY-1001, a lysine-specific histone demethylase 1A (LSD1) inhibitor, utilizing human SCLC tumor tissue on mouse models. Transcriptional analyses revealed an activation of NOTCH signaling which led to suppression of Achaete-scute homolog 1 (ASCL1) and SCLC tumorigenesis. Mechanistically, LSD1 was found to bind directly to regions of the NOTCH gene, repressing its expression and downstream signaling. Finally, complete and durable tumor regression occurred with ORY-1001 treatment in a chemoresistant PDX model.
In summary, the study showed that targeting LSD1 resulted in cell-signal disruption, which in turn caused shrinkage of the tumor. Further, this treatment appears to resolve tumors that have become resistant to chemotherapy, a very promising development.