Kdm1a, also known as Lysine-specific histone demethylase 1A (LSD1), is a histone demethylase that demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2) using flavin adenine dinucleotide (FAD) as a co-factor. It is involved in multiple biological processes, acting as an epigenetic developmental regulator, and has been implicated in carcinogenesis. It participates in pathways like Wnt/β-catenin, and its dysregulation can lead to abnormal cell growth and differentiation [1,4].

In cancer research, Kdm1a has been found to promote thyroid cancer progression and maintain stemness through the Wnt/β-catenin signaling pathway. Inhibition of Kdm1a using highly selective inhibitors like GSK-LSD1 can significantly inhibit thyroid cancer progression and enhance chemotherapy sensitivity [1]. In acute myeloid leukemia (AML), ORY-1001, a potent and selective KDM1A inhibitor, induces blast differentiation and reduces leukemic stem cell capacity [2]. In gastric cancer patient-derived organoids, genetic and pharmacological inhibition of KDM1A causes growth retardation, and its cancer-supporting functions center on repression of N-myc downstream regulates gene-1 (NDRG1) [3]. In ovarian cancer, knockdown of KDM1A or treatment with its inhibitors sensitizes cancer cells to chemotherapy drugs, and in an orthotopic intrabursal xenograft model, combined treatment significantly reduces tumor growth [5].

In conclusion, Kdm1a is a crucial epigenetic modifier involved in carcinogenesis. Studies using genetic and pharmacological inhibition models, including those similar to KO/CKO mouse models, have revealed its role in promoting cancer progression in various cancer types such as thyroid, AML, gastric, and ovarian cancers. These findings suggest that targeting Kdm1a could be a promising therapeutic strategy for treating these cancers.