So much for my commitment to write.... Just as I have started my blog account, my supervisor asked me to write a 10-page review article on his research -due in two weeks?!! Well, after 2 weeks of craziness, I thought that perhaps I should share a bit about what I have been writing.

Just to start- my supervisor works on engineering viruses to be used as therapeutic agents to destroy brain tumors.

The idea of using viruses began all the way back in 1980s, where scientists (including my boss) have started tinkering with lytic viruses- or viruses that replicates by lysing the host cell- to make them replicate and lyse only in cancer cells. One such virus that was extensively used is the herpes simplex virus (or HSV for short), which was chosen because it is asymptomatic- or not likely to make the subject sick. As it turns out, cancer cells have many features that make them more susceptible to HSV-mediated lysis. HSV could therefore be made cancer specific by deleting viral genes required for replication in normal cells, but not in cancer cells. Examples of such genes include thymidine kinase (deleted in thymidine kinase defective virus), and the neurovirulence genes ICP34.5 and ICP6 (both deleted in the multimutated virus called G207).

Using animal models bearing an implanted cancer cell-line derived tumor, it was shown in numerous studies that both viruses were extremely effective in destroying the implanted tumor.

When G207 was first tested in clinical trials for brain tumors, it demonstrated remarkable safety. But its tumor killing efficacy was nothing compared to what was observed in preclinical studies. As preclinical animal models of tumors are only predictive representatives of clinical tumors 10-60% of the time, it is not surprising that the greater complexity of clinical tumors could render them less susceptible to G207 attacks. Some scientists even demonstrated that viral gene deletions in G207 markedly attenuated their replication and dissemination in the tumor mass.

Consequently, much of the work in the last 20 years have been focused on not only improving G207, but also creating newer and more versatile HSV designs to eradicate the more complex clinical tumors.

One important advance in G207 design that has set the course of more recent HSV research is the development of Myb34.5 virus. This virus was created based on the G207 backbone, where the viral gene ICP34.5 was not deleted but rather expressed under the control of a cancer specific promoter Myb. The virus demonstrated considerable improvements in their replication and tumor killing efficiency, even via a less direct intravenous route. Not only that, but the virus was capable of going after cancer cells that have metastasized away from the parental tumor. Current research in our lab (as well as others) is now focused on designing better promoters (as well as other regulatory elements) to produce more effective tumor-killing viruses.

On this note, I could not help but reminiscent on how society (or more specifically Hollywood) have perceived the harebrained idea (or was harebrained before the 1980s) of using viruses as therapeutic arsenals against cancer. A good example of Hollywood's view is the 2007 movie "I am Legend" starring Will Smith, where the tumor-killing virus originally thought to be a cure for cancer turned out to be a horrific plague that turns humans into zombies ... again, this movie was a play on human technological folly and the terrible price that was paid by the entire human race.

Although the movie is exaggerating and wholly fictional, what rings true about this movie is that there is still a lot unknown about HSVs (or other tumor killing viruses). Although a number of clinical studies have suggested that the virus is relatively safe (so far), the results are still not a definitive answer. Because of the enormous expenses associated with clinical studies and the consequently sample sizes, the extent of the safety of the virus could still be a contentious issue in this field.