The following specific hypotheses were evaluated: (i) the expression of DNA-PK is increased in human ADPKD; (ii) the pharmacological inhibition of DNA-PK reduces cyst growth in vitro; (iii) inhibition of DNA-PK is selectively toxic to ADPKD cells; and (iv) DNA-PK inhibition enhances the sensitivity of ADPKD cells to sub-therapeutic doses of mTORC1 inhibition. This evidence concerns the gene PRKDC and autosomal dominant polycystic kidney disease.