It's possible I have a streak of hypochondria. When I suffered the Amazing Five-Day Headache from Hell last December, there was, I admit, a brief period where I genuinely feared I might have a brain tumor… until I went online and every single authoritative site informed me — with just a hint of exasperation — that chronic headaches are statistically very unlikely to be linked to the onset of brain cancer. I guess they get that particular Google search a lot. And of course, in my case, those sites were right — a visit to my doctor confirmed as much (and prescription strength headache meds put an end to the pain). But let's face it: the reason so many of us fear such things is because cancer is so prevalent in our society. Every one of us knows someone who has been diagnosed, suffered through surgery and/or chemotherapy, and in some cases, has died, from some form of the disease.
It's even more distressing when the patient is a child. Which is why we're taking time out at the cocktail party from posts about communicating science and the cosmos, and promoting Talk Like a Physicist Day, in order to promote a very different sort of event: the annual St. Baldrick's head-shaving fund raiser to benefit childhood cancer research, held this year on March 14 at Fado's Irish Pub in Chicago, among several other venues. I donated last year in support of regular CPP reader Matt Dick (he rewarded me by emailing a photo of his shiny new bald head). It's a fun, rowdy time, apparently, and all for a good cause. Makes me wish I lived closer to Chicago, despite those brutally cold winters.
Matt is participating again this year as a "Shavee," and I figured, in addition to making another small donation, I could help by spreading the word in hopes that some of my readers might be moved to also contribute to the cause. It's personal for Matt: his little cousin, Nathan, lost his fight with cancer (neuroblastoma, the most common of childhood cancers) last July, at the ripe old age of 6. It's too late for Nathan, but there are lots of other children out there who could be saved by a timely breakthrough in ongoing research. So check out the site, and if you feel moved, support Matt or one of the other Shavees.
There's some genuinely fascinating science going on related to cancer research. For instance, last year I wrote about the work of David Nolte's group at Purdue University developing a new holographic technique for imaging cancer cells to determine the effects of anti-cancer drugs on living tissue. Essentially, they can now measure the motion of organelles inside cancer cells to determine if they're living or dead, before and after the administration of anti-cancer drugs. (Organelles play a key role in fostering the out-of-control cancer cell division that so often proves fatal, so they are a primary target of drug therapies.)
New, more effective treatments are desperately needed. Matt told me about one prospective treatment that ultimately failed: injecting children with a neuroblastoma with T-cells drawn from mice exposed to a certain type of rodent virus, in hopes that the T-cells would kick into hyperdrive and aggressively attack the neuroblastoma. Alas, this didn't happen. In Matt's words, "While the mouse T-cells would go find the cancer cells, they just hung out at the scene not doing anything — the idle youth of the immune system, I suppose." (Matt clearly has a knack for creative analogy.) Now the researchers are trying a new twist: treating the mouse T-cells with radioactive elements, then injecting them into the neuroblastoma, in hopes of achieving small-dose, targeted radiation to the cancer site.
Targeted drug delivery continues to be a very hot topic, particularly for cancer research, because chemotherapy and other standard treatments quite frankly have nasty side effects. More targeted drug delivery can help reduce those side effects, because more of the drug finds its way to the cancer cells, rather than to surrounding healthy cells in the patient's body. Neurosurgeons can usually successfully remove as much as 99.5% of a brain tumor when they operate, but we're talking about brain tissue here, so they can't be as aggressive about removal as they might be in other, less sensitive areas of the body. There's always a few scattered cancer cells left over, which is where the targeted delivery of powerful anti-cancer drugs comes in.
There's been some recent exciting progress in this area with the development of "gliodel wafers" — essentially, disc-shaped implants infused with cancer-fighting drugs that are placed at the site where a tumor used to be just before the neurosurgeon closes everything up after removing a brain tumor. This means the drugs can dissolve and diffuse slowly into the surrounding brain tissue to kill any lingering cancer cells. The trick is getting past the blood-brain barrier, which is designed to keep stuff out. That's one possible reason why pharmaceutical agents don't appear to penetrate brain tissue uniformly — something that still puzzles researchers.
Brain cancers are especially challenging, as I discovered a couple of months ago when I chatted with George Lewis Jr., a researcher at Cornell BME who is working on finding ways to make targeted cancer drug deliver more effective. Some of the newer drugs are pretty darned powerful, and can easily stomp out those straggling cancer cells — provided the drug can reach them. Cancer cells are tricky: they migrate to other areas of the brain rather quickly after surgery. Sure, it's only a few millimeters to a centimeter, but it's just enough to elude the drugs, with nasty results. "In two weeks you have tumors reappearing, and in two months, the patient is dead," Lewis told me bluntly. And that's why brain cancers like neuroblastomas and neurofibromatosis are still the leading cause of cancer-related death in people under the age of 35: the few remaining cancer cells soon migrate beyond the range of the slowly diffusing drugs.
At last fall's meeting of the Acoustical Society of America, Lewis presented a paper on the use of acoustic pulses to help brain tissue absorb chemotherapy drugs faster — hopefully before the cancer cells have a chance to migrate very far — and also increase the range of diffusion. He and his collaborators (groups at Yale and Princeton) are using focused ultrasound to agitate the tissue matrices, enhancing permeability and making it easier for the drug to get into the brain tissue. Basically, they're massaging the brain tissue to open up the pores, since the brain is kind of similar to a sponge. (I held a "training brain" once while visiting a lab doing Alzheimer's research. It is indeed a spongy organ.)
Initial results from experiments with a horse brain indicate that with such a technique, the drugs do indeed spread further and faster into the tissue than they would by natural diffusion alone — a hundredfold further, in fact, which makes it very promising for future treatment of brain cancers. They're now carrying out a full study using live animals to see if they still get enhanced diffusion effects, and also to make sure a living creature can withstand the treatment.
Ironically, Lewis got the idea from an Indian study on using sono-poration for transdermal drug delivery, an older technique in which the drug is applied to the skin, and then ultrasound is applied which breaks down the skin surface so the drug can better permeate through. The Indian leather industry uses a similar technique to help dyes diffuse into the leather, resulting in a more uniform color. One of the things they discovered is that when surgeons remove the tumor and insert a drug disc into the cavity, there's a form of interface resistance that takes place, similar to surface tension on water. "It's because there's more tightly cohesive bonding between the cells at surfaces; they lock into each other," Lewis explained. "The sono-poration effect of ultrasound breaks down the interface and allows more rapid diffusion of drugs."
They're still not entirely sure what mechanism is actually at work in the technique. Some of Lewis's collaborators suspect that acoustic cavitation from microbubbles work to bloat the pores and open them up sufficiently so the drugs can diffuse through the tissue more effectively. Lewis thinks it might be primarily a mechanical effect related to the acoustic waves: "They go through the tissue as a compression wave, which oscillates the tissue and massages it to allow the drug more readily to diffuse through it." He likens it to how dentists will often massage a patient's gum when injecting Novacaine into the nerve because it helps push the drug around a bit to reach the nerve more quickly. "We're trying to rub the brain" using ultrasonic waves.
We want folks like Lewis and Nolte and the thousands of other researchers looking for new, improved ways to fight cancer to be able to continue with their work. One place to start is writing to Congress and complaining vociferously about the draconian cuts to science funding. Another is by participating in charity fund raisers like the ones offered by St. Baldrick's. Because someday, that cancer patient in dire need of cutting-edge treatment could very well be one of us.