While we were unable to identify any actionable mutation deemed causative of the emerging BRAF inhibitor resistance in Mel-DCC-11, functional drug testing revealed a number of promising therapeutic options, including HDAC-, microtubule-, topoisomerase-, or EGFR-inhibitors and drugs targeting the PI3K/Akt/mTOR signaling pathway, which have been described to overcome drug resistance in mutant BRAF melanoma cells (Dratkiewicz et al, 2019; Wang et al, 2021; Misek et al, 2022). Here, AKT1 is linked to melanoma.