Using a CRISPR-based library screen, Lu et al. identified NF1 and DUSP9 as key drivers of lenvatinib resistance in HCC and further demonstrated that NF1 loss reactivates both the PI3K/AKT and RAS/MAPK pathways, whereas DUSP9 loss selectively activates the RAS/MAPK pathway, collectively promoting resistance [135]. The gene discussed is AKT1; the disease is hepatocellular carcinoma.