The key findings were the following: (i) the expression of genes of all three subunits of the DNA-PK complex was increased in human ADPKD transcriptome, as well as localized to cyst lining epithelial cells in human ADPKD; (ii) long-term inhibition of the catalytic activity using specific small molecule inhibitor NU7441 in MDCK 3D cysts reduced MDCK growth by up to 52%; (iii) human ADPKD cells do not exhibit synthetic lethality to DNA-PK inhibition by NU7441; and (iv) finally, the increased sensitivity of human ADPKD cells to TORC1 inhibition was enhanced by combination treatment with NU7441. This evidence concerns the gene PRKDC and cyst.