As mentioned in class, parvoviruses are promising candidates for cancer therapy since they do not cause severe disease and have been shown to kill cancer cells. The mechanism by which parvoviruses are able to attack cancer cells has thus far been unclear. Recently however, researchers at the German Cancer Research Center were able to find a potential oncolytic mechanism by which parvoviruses act.
Using experimental mice, these researchers discovered that parvovirus binds to an enzyme called PDK1 kinase, which functions as a switch in important cell processes including cellular growth. This binding leads to the activation of PDK1.
Interestingly enough, in healthy people, the parvovirus-PDK1 kinase activation pathway is not seen. However, those with cancer (particularly those with glioblastoma) had permanently activated PDK1. In in vitro studies with constitutively active PDK1, parvoviruses were able to exploit the PDK1 pathway and replicate inside PDK1 cells, as they were in mice. Such results are extremely exciting because they open the door for in vivo research studies that may show a link between parvovirus replication in PDK1 and cancer progression.