Interactions between adenovirus proteins and the p53 pathway: the development of ONYX-015.
dl1520 (ONYX-015) is an adenovirus mutant that lacks the E1b 55K gene. As a result it cannot neutralize p53. Therefore dl1520 should only grow in cells that lack p53, and should replicate selectively in cancer cells. However, there is no correlation between replication and p53 status, in cancer cells. This is for two reasons: (1) E1B 55K has additional functions, that are necessary in some tumor cells and not in others. (2) p53 function can be lost by alternative mechanisms such as loss of p14ARF. In normal cells, dl1520 induces p53, and is generally strongly attenuated for replication. ONYX-015 is currently being tested in clinical trials, and is a promising new therapeutic agent in cancer.
McCormick
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Cancer Research Institute, UCSF Cancer Comprehensive Cancer Center, San Francisco, CA 94115, USA. mccormick@cc.ucsf.edu
D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D016159:Tumor Suppressor Protein p53