E1B55K-Deleted Adenovirus (ONYX-015) Overrides G₁/S and G₂/M Checkpoints and Causes Mitotic Catastrophe and Endoreduplication in p53-Proficient Normal Cells

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

“…Nevertheless, the differences in action of DTIC may be due to different concentrations used (2 mM vs. 5 mg/ml). In addition, tumor cell lysis caused by oncolytic adenovirus has been previously shown to block the cell cycle at the G 2 /M phase, 10,23 which is consistent with our data and caused a distinct accumulation of cells in S and G 2 phases. The combination, however, did not lead to an obvious cell arrest in a certain phase.…”

p53 gene in treatment of hepatic carcinoma:Status quo

“…As HCC cells with p53 defects have lost their cellular surveillance mechanisms, oncolytic viruses interfering with the main surveillance pathways such as those controlled by p53 [73] , could replicate selectively in them and cause lysis. E1A gene of adenovirus is an apoptosis-inducing gene and E1B gene of adenovirus is an apoptosis-inhibiting gene.…”

“…Because of a deletion in E1B, the 55-kDa E1B protein is not expressed and the mutant adenovirus, termed ONYX-015 [83] , is able to replicate only in wt-p53 deficient cells. The E1B55K-defective adenovirus ONYX-015 is a prototype [73,82,83] of oncolytic viruses and can selectively replicate in and kill p53-deficient HCC cells, the success of cancer gene therapy is not promising unless it is carefully designed based on the biology of a specific [84] tumor type. To enhance the efficiency of such oncolytic viruses, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene has been constructed for antitumor activities against HCC, and termed as CNHK200-mE [85] .…”

“…Since unlike most other tumor suppressor genes, mt-p53 is over-expressed in tumor cells, a promising approach involving reactivation of tumor-suppressing function to mt-p53 [21,25] . Further understanding of the mechanisms of how to restore p53 activity, may lead to discovery of more potent analogs and new strategies [11,73,91] for p53-targeting in tumor therapy. More genes previously unknown have been identified that are involved in the regulation of p53 transcriptional activity and their over-expression inhibits p53 target promoters and p53-mediated apoptosis, suggesting that these genes play a role as p53 inhibitors and may have oncogenic activity [98] .…”

“…Inhibition of cell growth and apoptosis can be achieved [55] . Oncolytic viruses [73,74] are a number of defective viruses, which cannot replicate in normal cells but are able to grow in tumor cells, finally leading to their lysis.…”