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Cancer

Has the smart bomb been defused?

Nature volume 395, pages 13–15 (1998)Cite this article

A goal of cancer research is to develop therapies that can selectively kill tumour cells without adversely affecting normal cells — this is crucial for both the short-term comfort and long-term survival of patients. One such agent is a genetically engineered adenovirus from ONYX Pharmaceuticals, called ONYX-015, which is thought to selectively replicate in (and kill) tumour cells deficient for the p53 tumour-suppressor pathway, having little toxicity to normal cells1,2. Because p53 is mutated in over half of all human cancers, and is probably functionally deficient in many others owing to mutations in associated genes, ONYX-015 could prove useful in treating a range of tumours. But a report by Hall et al.3 in Nature Medicine raises a serious question about the efficacy of this virus.

In stark contrast to initial results published by ONYX1,2, Hall and colleagues suggest that adenoviruses require p53 to kill cells efficiently. They propose that ONYX-015 would selectively destroy normal cells. Yet the claims by both groups about the dependence on p53 are subject to alternative interpretations, so no definitive conclusions can be reached at present.

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Figure 1: Influence of adenoviral E1A/E1B proteins (blue) and cellular p53 status on viral replication and cell death.

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  1. the Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 9,000 Rockville Pike, Bethesda, 20892-4255, Maryland, USA

    Steven P. Linke

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  1. Steven P. Linke
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Linke, S. Has the smart bomb been defused?. Nature 395, 13–15 (1998). https://doi.org/10.1038/25595

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