Collectively, these findings demonstrate that through the intratumoral dispersion of the oAd via multifaceted mechanisms (increased internalization into cancer cells via upregulating key factors in CAR-dependent or dynamin-dependent clathrin endocytic pathways, ECM destruction, and induction of apoptosis), the combination of ECM-degrading oAd and HDACi is an effective strategy to maximize the potent antitumor efficacy of each monotherapy. This evidence concerns the gene DNM1 and cancer.