Utilizing a first-in-class small-molecule PU.1 inhibitor that specifically and allosterically interfere with PU.1-chromatin binding [30], we found “KAC” cells were significantly more sensitive to growth inhibition, compared to control “KC” and “KPC” cells (Figure 7J), presenting PU.1 as another synthetic lethal target in ARID1A-null PDAC cells. This evidence concerns the gene SPI1 and keratoconus.