Foxo TRAIL
Dr. Wafik S. El-Deiry and colleagues at Penn State University developed a new drug, TRAIL-inducing compound 10 (TIC10). What is TRAIL and what’s the big deal?
TRAIL is tumor necrosis factor-related apoptosis-inducing ligand. It’s a protein in our immune system that induces apoptosis (programmed cell death) in tumors. The problem with recombinant versions, i.e., man-made versions intended to be given as an anti-tumor drug, is that TRAIL has a short half-life in serum and it has poor biodistribution (it doesn’t readily cross the blood-brain barrier). So TIC10 induces TRAIL and because TIC10 can cross the blood-brain barrier, it appears to be more efficacious than trying to administer TRAIL directly. Since TRAIL is part of the immune system, boosting it with TIC10 is thought to be less toxic than traditional chemotherapy. It remains to be seen what side effects there are from TIC10 itself.
What is FOXO and what does it have to do with this story? The TRAIL gene is transcriptionally regulated by Foxo3a. The FOXO3, also called, Forkhead box 03, is characterized by a distinct fork head DNA-binding domain and is likely a trigger for apoptosis.
Before you get too excited, the paper notes that the TIC10 group only had a 6% increase in survival compared to a more traditional anti-vascular drug, in a mouse model.
News blurb from Nature.com
Small-molecule drug drives cancer cells to suicide
Full article in Science Translational Medicine behind paywall.
Fox image from Dan Dinu: http://goo.gl/adqSb
#ScienceEveryday when it isn’t #ScienceSunday
February 8, 2013
The content is
waya bit over my head, but it looks to me as if Firefox is having trouble paying royalties on its logo.February 8, 2013
Thomas Kang I wrote this before bed so I didn’t re-read it enough times to see if I made it suitable for the lay audience. I’m not gifted like Rajini Rao
February 8, 2013
I’m not boasting but it’s probably good to be boosting the immune system with TIC10 (penultimate sentence of para 2) 😉
February 8, 2013
only 6%? oh .. 0.0
February 8, 2013
Another way to look at that 6% number is that it is at least as good as a standard GBM drug on the market. The trick may be to find synergistic combinations that work a lot better together to increase survival.
February 8, 2013
It is promising and exciting for sure but not a panacea.
February 8, 2013
My mind has moved now from the troubles facing the Firefox in the image to boasting with TIC 10.
I have some TIC10. I have some TIC10. Nya nya nya nya nya nya!
< Sighs to self, wishing he could contemplate post at a higher level. >
February 8, 2013
Thomas Kang , if you ignore the acronyms (which are often of limited use anyway), it’s quite straightforward. TRAIL is a small protein that binds to “death receptors” on the surface of cells and can set off a cascade of events leading to apoptosis or “programmed cell death”. Because it is a protein and not a small molecule drug, it is not going to cross the membranes in the brain blood vessels to act on gliomas (brain cancer). What these researchers did is to find a small molecule that can cross the blood brain barrier to turn on the expression of TRAIL, which can then kill off tumor cells.
February 8, 2013
Rajini Rao Is what you’re saying in any way related to this story (http://goo.gl/ettt0)? I was able to make easy sense of this, which sounds to me like a similar principle at work.
February 8, 2013
Thomas Kang , not really 😛 The only thing in common between the two stories is that they both kill cancer cells by apoptosis. The one you found uses nanoparticles to deliver a death-inducing protein to cancer cells. Chad’s story is about turning on a gene that naturally kills cells. Did you read the Nature views article in Chad’s link? That is well written, IMO.
February 8, 2013
I did read it after tracking down the nanoparticle story. I found it a little easier to follow than Chad’s summary, I presume because Chad is targeting a more specialized audience.
What made me confuse this one with the nanoparticle story was your comment about crossing the blood barrier. I’m getting the sense that whereas the link I posted describes protecting the apoptosis trigger with a nanoparticle coating so that it reaches the targeted cancer cells, in this case the issue (or one of the issues) is that of having the apoptosis-inducing mechanism small enough to penetrate the blood-brain barrier.
Am I getting closer?
February 8, 2013
Yes, you’re absolutely correct 🙂
February 8, 2013
Yay! Science is accessible to people like me, after all!
I feel like the kid whose face finally lights up in recognition, no longer feeling the need to make up for his own ignorance by disrupting the class with silly jokes. ^
February 8, 2013
Sorry Thomas Kang I was intrigued by the serendipity of posting the fox images then stumbling on a cancer article that talked about Foxo and TRAIL. It seemed too good to pass up. I was hoping that people would read the Nature.com news blurb to get the main story and yet appreciate the connection of the full article to the picture.
February 8, 2013
Not a problem at all, Chad; I’m used to seeing stuff way over my head with many of the links in Mark Bruce’s weekly summaries as well as other science posts here and there. I still like them and like taxing my brain. The specialized science jargon is always a challenge, but I figured in this case you were deliberately focusing on communicating at a more specialized level, given, I presume, how close some of this stuff is to your research.