To determine whether SHPK inhibitors can reduce the generation of venetoclax resistance in our in vitro system, we employed SKI-II, which inhibits both isoforms of SHPK, and opaganib, a SPHK2 inhibitor that is currently in Phase 2 clinical testing in patients having cholangiocarcinoma (NCT03377179) or prostate cancer (NCT04207255). This evidence concerns the gene SPHK2 and cholangiocarcinoma.