E47-inducible cell lines were generated by infection with
a retroviral vector expressing E47 fused to a tamoxifen-inducible
modified estrogen receptor (MER).
The way this was done was really clever: it uses a virus that causes cancer to treat cancer. Specifically, the retroviral vector is an engineered strain of Moloney Murine Leukemia Virus (MoMuLV), which can cause leukemia in mice (it is not known to cause disease in humans, though retroviral infection does carry at least a small risk of mutagenesis). The viral vector inserts a gene that expresses the protein E47, which acts in a variety of ways to make cancer cells revert to acting like healthy cells.
This is an exciting idea, though as the press release notes, "we are screening for molecules—potential drugs—that can induce overexpression of E47." That's a way of noting that retroviral vector gene therapy is in its infancy, and that it would be much better if we could find a small molecule instead.
These findings prompted us to ask whether
the growth arrest and acinar gene expression induced in vitro
might be sufficient to diminish the tumor-forming potential of
these aggressively growing cells. Indeed, temporary induction of
E47 for 2 to 8 days in vitro produced stable cell cycle arrest and
trypsinogen expression in transplanted human PDA cells. It will
now be of interest to investigate the effects of E47 on the growth
dynamics of established tumors.
And also the above- established tumors notoriously mutate and become genetically heterogeneous over time, greatly increasing the chances that at least some of the cancer cells are resistant to whatever line of attack you throw at them. Cancer cells that have mutant forms of E47's targets wouldn't be reprogrammed. Still, any advance against pancreatic cancer is highly welcome.