If ESET can be blocked, retroviruses would become dramatically more active, thus either killing the cancer cells hosting them or flagging them as targets for the immune system.
Leung, who was co-lead author with a graduate student at Kyoto University in Japan, has devoted his studies at UBC to the growing field of epigenetics -- changes to the genome that do not involve changes to the underlying genetic code. Such changes determine whether or not a gene is expressed.
All cancer drugs share a problem: They penetrate just a few cells into the tumor. Now a team of biologists has identified a molecule that helps cancer treatments dive deep into tumors, at least in mice. The approach still needs to be tested in people, but if it pans out, it will circumvent one of the biggest challenges in the field. “This has huge implications for cancer therapy,” says David Cheresh, a tumor and vascular biologist at the University of California (UC), San Diego, who was not involved in the work.
Tumors keep drugs at bay in two ways. First, their vessels are not leaky enough to allow drugs inside. And second, they have high hydrostatic pressure. This means that fluid tends to flow away from tumors, not toward them, and that “any drug has to swim upstream, if you will,” says Erkki Ruoslahti, a cell and tumor biologist at the Sanford-Burnham Medical Research Institute in Santa Barbara, California. Last year, Ruoslahti and two scientists in his lab, Kazuki Sugahara and Tambet Teesalu, reported on a new peptide, a small molecule called iRGD, that seemed to do a good job of getting inside tumors when it was anchored to a cancer drug.
Drugs failing to get into tumors “is a huge problem for cancer in general,” especially when disease appears in the brain, which is even less accessible, says Zena Werb, a cell biologist at UC San Francisco. Werb cautions, however, that “it’s rather early” to tell how promising iRGD is. Cheresh points out that one risk is that the peptide could spawn new metastases by opening up tumor blood vessels and helping cancer cells to slip out. Still, they agree that if iRGD’s safety and effectiveness pan out, it could revolutionize cancer treatment for patients with all sorts of tumors. Ruoslahti is pushing it forward; he and his colleagues have filed patent applications on the peptide and are now in discussions with drug companies about testing it in humans.
In their article published in the open-access journal PLoS Pathogens, Dr. Cohen's team explains how the Vpu viral protein prevents the expression of Tetherin, a host factor inhibiting HIV-1 release, on the surface of infected cells.
Thus, if researchers manage to develop small molecules that prevent Vpu binding to Tetherin, this would restore one of the natural defence mechanisms that prevent the production, transmission and spread of HIV-1.
The study by Dr. Cohen's team allows a better understanding of the strategy used by HIV-1 to facilitate its transmission and its spread in humans. "Tetherin is a cellular protein that captures viruses forming at the surface of infected cells, thereby preventing viral transmission and spread. This antiviral protein, whose production is triggered by interferon, is an effector of the innate immune response against viral infections. However, viruses, and especially HIV-1, have evolved and developed mechanisms that antagonize this restriction factor. In fact, we have discovered how the Vpu protein neutralizes Tetherin, and as such stimulates HIV-1 production," stated Dr. Éric A. Cohen.
