The gene, p53, is mutated in about half of all human cancers (an event directly implicated in tumour progression). Hence, a way of killing such cells offers the attractive possibility of treating multiple cancer types with one drug.
The human adeno-associated virus (AAV) selectively induces cell death in p53-defective cells, Peter Beard and his colleagues of the Swiss Institute for Cancer Research (ISREC) in Epalinges, Switzerland, have now discovered. Cells retaining their copy of p53 instead halt cell division.
Even AAVs engineered to lack all genes and containing only hairpin-looped DNA ends cause cell death. This suggests that the viral DNA structure mimics DNA damage in the cell.
| Human adeno-associated virus induces cell death in p53-defective cells|
Cells have very sensitive sensors for DNA damage that can activate repair mechanisms or drive them to suicide to prevent mutation accumulation and hence potential oncogenic transformation.
Tumours in mice were also reduced by injection of the virus, the team found.
Continued research into strategies to exploit p53 should eventually lead to one that is fruitful.
"Each strategy has the potential to benefit millions," say Bert Vogelstein and Kenneth Kinzler at the Howard Hughes Medical Institute and Johns Hopkins Oncology Center in Baltimore, Maryland, in an accompanying News and Views article.