LSD1 & Cancer

Lysine specific demethylase 1 (LSD1, also known as KDM1A) is a histone modifying enzyme that removes methyl groups, is therefore an “eraser”, and by doing that regulates the expression of many genes important in cancer progression and cell proliferation.

Aberrant expression of LSD1 has been shown in many types of cancers. Among others, LSD1 expression is upregulated in bladder, small cell lung, and colorectal cancer when compared with the corresponding healthy tissues. LSD1 has also been shown to be overexpressed in some breast cancers and may function as a biomarker of the aggressiveness of the disease.

One of the cancers where the function of LSD1 is better understood is in acute leukemia. Particularly, in a subset of Acute Myeloid Leukemia and Acute Lymphoblastic leukemia, LSD1 is crucial for the function and maintenance of the leukemic stem cells, a subset of malignant cells that is believed to be the ultimate reason for relapse in those patients. LSD1 inhibition might be a therapeutic solution to avoid those relapses.

Small cell lung cancer (SCLC) is a very aggressive tumor with currently very limited therapeutic options. A SCLC subtype (known as neuroendocrine phenotype) has been found to be very sensitive to LSD1 inhibition. Our LSD1 inhibitor iadademstat is capable of causing a molecular signaling rearrangement in tumor cells, re-expressing a very important control gene, Notch-1, which in turn is able to "switch off" an oncogene that has been described as the main cause for tumor progression in this type of cancer. Experiments in animals with very aggressive tumor cells obtained from relapsing SCLC patients have provided very encouraging results regarding the potential of iadademstat as a therapeutic alternative in these tumors.