Fantastic Voyage into Angiogenesis

April 17, 2009 12:36 PM

"Angiogenesis is critical for tumors to grow beyond a few millimeters, and for cancer to metastasize to other parts of the body. Cancer cells use the blood vessels as conduits to other areas of the body, where a single cell can set up camp and begin forming a new tumor. Stop angiogenesis, and you stop cancer." (via)

I'm no scientist, but I think the Flash presentation at the second link is simply too stunning to pass up.

posted by monospace (35 comments total)

I can't get it to load completely...it keeps hanging on "loading slide 6". Just me?
posted by jquinby at 12:48 PM on April 17

The video is on the (via) link as well. It's still very slow to play for me.
posted by odinsdream at 12:50 PM on April 17

One moment. I have to pick my jaw off the floor. The Flash takes a while to load but is seriously worth it.
posted by Electric Dragon at 12:54 PM on April 17

Switched to IE, works. Very cool stuff.
posted by jquinby at 12:54 PM on April 17

This reminds me of The Inner Life of a Cell. Hooray for high-budget scientific visualization!
posted by CaseyB at 12:54 PM on April 17

Some background including the fairly popular drug. There's a lot out there about VEGF and VEGFR1 / R2 now.
posted by a robot made out of meat at 12:56 PM on April 17

Yeah, CaseyB, when I saw that video you linked, I was like, damn! those stoners were right, there are worlds within worlds on my fingernail.
posted by StickyCarpet at 1:00 PM on April 17

That is really nice work.
posted by Mister_A at 1:07 PM on April 17

wow I really wasn't expecting to be so impressed with the flash stuff, but that is on a whole nother level!!

also, very interesting and informative.
posted by supermedusa at 1:09 PM on April 17

Wow, nicely presented material. Thanks for posting this.
posted by maxwelton at 1:16 PM on April 17

Damn, now that is how you use Flash.
posted by Brandon Blatcher at 1:26 PM on April 17

That is some hot shit medical visualization.

Brought to you by the Umbrella Corporation?
posted by gwint at 1:29 PM on April 17

Stopping angiogenesis also stops wet age-related macular degeneration.
posted by benzenedream at 1:30 PM on April 17

Wow, this is an amazing work of art. The narrative medical-babble just adds to the authenticity. Someone should make a movie or game out of it.
posted by stbalbach at 1:42 PM on April 17

I edit scientific manuscripts, so I see a lot of the latest stuff. I've gotten the impression that anti-angiogenesis therapies are looking very promising. But this will all have to be sorted out by further research.
posted by Turtles all the way down at 1:44 PM on April 17

1:10 into the first presentation, it's a cancer mosh pit. Brilliant. Well, the whole thing, really.
posted by maudlin at 1:45 PM on April 17

Neat marketing, here's how they pay for the fancy flash animations:

"For colorectal cancer, Meyer wrote in the New England Journal of Medicine that bevacizumab extended life by 4.7 months (20.3 months vs. 15.6 months) in the initial study, at a cost of $42,800 to $55,000. The addition of bevacizumab to standard treatment can prolong the lives of breast and lung cancer patients by several months, at a cost of $100,000 a year. "

Bevacizumab is produced by Genentech and not Amgen, but can't imagine their anti-VEGF drugs are produced at a cheaper cost, these are complex proteins that don't lend themselves well to industrialized processes yet. Genentech has to genetically engineer mice to produce the proteins they want.

Does anyone know more about manufacturing these drugs? I'm guessing if they're genetically engineering mice as the first step in the process, we're nowhere near brewing these in a big vat.
posted by geoff. at 1:49 PM on April 17

Why can't they just stick a plasmid into something that grows well in a vat?
posted by fleetmouse at 2:00 PM on April 17

You know what else appears to help stop vascularization?

(Hint: it's cheaper than bevacizumab)

Why do so many commercial drug names look like if you read the name backwards, it might make demons appear?
posted by caution live frogs at 2:56 PM on April 17 [1 favorite has favorites]

Not to be a damp rag, but, well, stop angiogenesis and you stop a lot of things. I'm not sure that antiangiogenesis the end-all and be-all of treating cancer, but it does help. Existing blood supplies can be used by metastases, though. And these drugs are extremely profitable for big pharma. However, prevention is better than toxic treatments. Stop mutations and you prevent cancer, for sure.
posted by Mental Wimp at 2:58 PM on April 17

I hope they come up with a good menacing name for these anti-angiogenesis therapies, like they did for radiosurgery with CyberKnife. Yeah, put a fucking shiv in cancer.

Thanks for the post.
posted by Mountain Goatse at 3:00 PM on April 17 [2 favorites has favorites]

I suspect that cancer treatment will ultimately pack this as one part of a regimen. You really want new blood vessels. But if you could stop their production for a little while, while you received a dose of your own immune system, trained to attack a biopsied sample of tumor and fed back to you, at the same time you're starving a bit so that the chemo takes slightly better hold, the cumulative effects might have a better chance to attack on all fronts rather than relying on One Magic Pill.
posted by adipocere at 3:03 PM on April 17

Over the years working on oncology trials, you get to see some pretty awesome drug names and abbrevs. I worked on a trial involving Bevacizumab, in fact. Other favorites just for mouth/eyefeel:

Zevelin
Rituximab
Tositumomab
Solumedurol
Bortezomib

And my two favorites (didn't work on these trials, but a colleague did):

Hyper-CVAD
and
ProMACE-CytaBOM

Luke, get in the Hyper-CVAD! I'll use my ProMACE to hold off the stormtroopers until you can CytaBOM them back to hell!

*pew pew pew*
posted by Skot at 3:14 PM on April 17 [7 favorites has favorites]

I haven't watched it all yet, but so far this is the best science fiction movie I've seen in years.
posted by OmieWise at 3:19 PM on April 17

Amazing stuff.

Pericytes look a lot like headcrabs. I had a burning desire to start whacking them with a crowbar. A tiny, tiny crowbar.
posted by ocha-no-mizu at 4:44 PM on April 17 [2 favorites has favorites]

This stuff fascinates me. I'm a peon at a big pharmaceutical company. I started back in school for bioinformatics a couple of years ago. The first year Biology class disabused me of that notion, so I changed my major to something more CS-centric. I still love biology related stuff, even if only in a hand wavey kind of way.

The animation is fantastic, but don't forget that Amgen (whom I don't work for) is laying the groundwork here to sell a new drug. Even though big pharma is TEH EVIL, I am glad to see that at least some of us are working on cancer.
posted by double block and bleed at 7:06 PM on April 17

Geoff., I know a little about how these proteins are manufactured, having worked on a therapeutic mAb (which bombed out in Phase III trials, alas). It's too painful to watch the Flash show - all stuttery due to my sucky internet connection - so I don't know how they're engineering the mice here. If you could summarize that, I could try to answer your questions. There are several things they could be doing with the mice, so I don't want to just start blathering.
posted by Quietgal at 7:13 PM on April 17

maybe more than i ever wanted to know about cancer (or find myself able to comprehend), but, wow! what an amazing presentation. really amazing!
posted by RockyChrysler at 7:34 PM on April 17

TumorShiv would be a fab medical device/technique name, MG.
posted by NikitaNikita at 8:52 PM on April 17 [1 favorite has favorites]

So....am I Meg Ryan now?
posted by doobiedoo at 5:15 AM on April 18

*in*, in Meg Ryan, christ it sounds creepier on isolated correction
posted by doobiedoo at 5:16 AM on April 18

Things I've learned:
1. Blackberries are evil.
2. Pericytes are not parasites.
3. Blood vessels are created by jellyfish polyps.
4. muh-TAS-tuh-sis

I wonder how much this cost to produce, and whether that money could be put to better use.
posted by Sys Rq at 8:54 AM on April 18

(Still: Wow!)
posted by Sys Rq at 8:56 AM on April 18

Why can't they just stick a plasmid into something that grows well in a vat?

Inside a cell is where proteins are made. But it's a process rife with complications.

Some proteins migrate to and latch on to the cell's surface ("cell membrane"). Other proteins float inside the cell, get packaged into vesicles or "bags", or latch on to internal cellular "walls" like the Golgi bodies or endoplasmic reticulum.

Where the protein product ends up after the cell makes it is what determines whether the vat or bioreactor process can isolate the protein (i.e. whether it can be done, and whether it can yield product at a rate and purity that is cost effective).

Another determinant is whether the protein drug is a precursor. Like mixing epoxy from two different components that are themselves not adhesive, precursors are not useful as drugs themselves. They require post-translational modification, such as phosphorylation, cleavage, or other chemical changes, before they are active and useful as a drug therapy.

A good historical example is insulin, which requires three cuts made before it can regulate blood sugar. So it's not enough to simply put the insulin gene into a plasmid and grow it in a vat. There needs to be some tailoring after manufacture to make a good fit.

A drug made for humans (who are eukaryotic organisms) may require these kinds of alterations to be made active. For that reason, these drugs are sometimes not good targets for recombinant bacteria, because bacteria are prokaryotic and lack the machinery to coordinate and complete certain kinds of eukaryote-specific chemical changes.

To solve these problems, in place of bacteria, labs use mice or other eukaryotes that are readily genetically engineered and easy to reproduce, and make it easier and more cost effective to harvest drug product.
posted by Blazecock Pileon at 9:14 AM on April 18 [2 favorites has favorites]

Attacking tumors through the angiogenesis pathway is old, probably as old as some mefi users. Making it work, that is so new that it doesn't exist yet. Cancer is a disease that we will lick, but it is a slow slog and many of us reading this thread now will be felled by cancer before the fix is in. (by the way, that cascade slide was so much fun. we keep thinking that once we map in gross a cascade in the body that all we need to do is interrupt it at a critical point to change the outcome to one we prefer. Then, we see how the body has feedback cascades upon its feedback cascades to thwart most of these simplistic attempts)
posted by caddis at 7:52 PM on April 18 [1 favorite has favorites]