Guided by the genetic alterations, the efficiencies of retinoic acid (RA) and a PI3K inhibitor were evaluated in ACC PDX models harboring both MYB fusion and PIK3CA amplification/mutation. Combination treatment of the PI3K inhibitor and RA demonstrated remarkable inhibition of tumors in PDXs harboring both PIK3CA mutation/amplification and MYB-NFIB fusion gene in vivo and in vitro.