Fig. 4
From: Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature
KDM6A/KDM6B inhibition in colorectal cancer. KDM6A/B expression negatively correlates with survival in patients with colorectal cancer (CRC), suggesting a pathogenic role for these H3K27 demethylases. Inhibition of KDM6A/B with GSK-J4 attenuates the hyperproliferative, apoptosis-resistant and stem cell-like phenotype of CRC cells and promotes their enterocyte differentiation. GSK-J4 also inhibits the malignant transformation of intestinal stem cells, which reside in the intestinal crypts and are thought to be the source of most CRC cells, promoting instead their differentiation into enterocytes. In addition to its direct tumoricidal activity, GSK-J4 heightens the sensitivity of colorectal cancer cells to the chemotherapeutic agents fluorouracil and oxaliplatin. This figure was created in BioRender.com