New research on viruses may translate into new therapies to beat cancer, scientists say.
Molecular biologists at the Salk Institute have uncovered a previously unknown mechanism that allows adenoviruses — culprits behind the common cold as well as other illnesses — to beat the body’s immune system. Since adenoviruses and tumor growths both overcome our natural cellular defenses in a similar way, understanding one disease process can give us good clues for ways to fight the other, scientists hope.
Here’s how it works. Previous research has shown that the “p53” protein is both a tumor suppressor, preventing cancer growth, and also important for keeping adenoviruses in check. When cancer invades one of the body’s cells, p53 will try to kill the cell outright to prevent the cell from being overrun. Adenoviruses also need to overcome p53 to replicate. Tumors and adenoviruses, therefore, have both adapted mechanisms of their own to knock out p53.
Scientists already knew about one mechanism by which adenoviruses can repress p53 function. But in the newly released research, published in the journal Nature, the Salk scientists analyzed adenoviruses with several induced mutations and discovered a second, previously unknown repressor of p53. That gives them a better idea of how adenoviruses overcome the body’s immune response to replicate successfully — and it hints at better ways to create new, genetically engineered viruses that would target and destroy tumors without otherwise causing harm to humans.
It sounds complicated. But Kevin Ryan, a molecular biologist and cancer researcher who was not involved with the study, explains why this finding is so important. Writing in an editorial published in the same journal issue as the original research, he says:
Undoubtedly, the greatest significance of this study will be its contribution to devising strategies to treat cancer. Adenoviruses must inactivate p53 so that they can replicate and subsequently induce the breakdown of the infected cell. Because many tumours lack p53 function, researchers have engineered viruses that lack E1B-55k [the previously known mechanism to wipe out p53] with the idea that these viruses would replicate selectively in tumour cells lacking p53 but not in normal cells, eventually leading to the death of the tumour cells.
In other words, scientists have already tried to engineer new viruses that would thrive only in tumors, killing off cancers. If cancer invades a healthy cell and wipes out the p53 function, then the lack of p53 allows the adenovirus to go in and take over the cell. With some genetic engineering to make sure that the adenovirus has no ability to repress p53 itself, the specially created virus should be of little threat to healthy cells — only a threat to the cancerous cells, where p53 function is suppressed.
Viruses like this have already been created. Ryan continues, however:
Although these engineered viruses have proven to be therapeutically beneficial, their replication does not seem to depend on the p53 ‘status’ of the cell.
They also weren’t as successful as treatments as people might have liked.
[The new] finding that [the second, newly uncovered p53 repressor] E4-ORF3 also, at least partly, inactivates p53 function provides an explanation for why this would be the case. Following on from these insights is the exciting prospect that adenoviruses lacking both [of the p53-blocking mechanisms] could be selective and even more potent anticancer agents than viruses lacking just E1B-55k.