Killing brain cancer with electricity

Cancer is a disease that involves cells dividing faster than they should (check this out for a review of how cells divide) along with many other complicated processes.  But if you simplify cancer to this one concept – cells dividing too fast – then you can think of interesting ways to kill cancer cells by targeting cells that are dividing quickly.  In fact, many (if not most) current cancer treatments do just that  – they create too much DNA damage for the cancer cells to handle, so the cancer cells kill themselves. There is a bit of a problem with this though – cancer cells aren’t the only cells that are quickly dividing.  Hair follicles, cells in the lining of the gut and blood cells all also divide quickly.  This is why non-specific cancer treatments like chemo that go throughout the body also end up killing these fast dividing cells, which is why cancer patients often lose their hair, have low blood counts and have gastrointestinal issues.


By Kelvinsong (Own work) [CC BY 3.0], via Wikimedia Commons

Wouldn’t it be great if the cell division part of cancer cells could be more targeted, less toxic, and avoid many of the difficult side effects from cancer treatment?  Scientists are working on a number of different treatments that do just that, but in this post I’m going to talk about one that is particularly interesting because it’s being used in clinical trials in our backyard at the Barrow Neurological Institute to treat glioblastoma multiforme (abbreviated GBM). GBM is the most common form and aggressive adult brain cancer. GBM has a terrible prognosis – with 50% of patients diagnosed dying within one year and 90% dying within 3 years. Standard treatment involves surgery to remove the tumor, and then radiation and chemotherapy treatment.  Treatment is difficult, and because this is a brain tumor, there are additional challenges involving brain damage from surgery, radiation and/or chemo and getting drugs through the blood-brain barrier into the brain tumor.


Thanks to MedGadget for the image

A new treatment called NovoTFF (TFF stands for Tumor Treating Fields) goes directly after the dividing GBM cells. Receiving FDA approval in 2011, it is a device that is worn as a cap (see image at left) and uses a battery pack that can be worn in a backpack to create wave-like electronic fields that penetrate the brain.  These fields disrupt the spindles that are responsible for separating the chromosomes during the cell cycle (see image above). There is also some evidence that these electric fields disrupt the cell membrane of dividing cells as well. Since the GBM cancer cells are dividing, they will be most likely to have their cell cycle disrupted and the cells’ natural response to this kind of major disruption is to die.  This treatment has amazing advantages.  Because it’s worn outside the body, NovoTFF isn’t invasive like surgery.  It’s also just worn on the head so it won’t have side effects like the ones from treatments that go throughout the body.  Also, the electric fields won’t affect cells that aren’t dividing (like most brain cells), so this treatment is less likely to cause damage to the non-cancerous brain cells.  But does it work?  Yes! In multiple clinical trials, this treatment was shown to slow the growth of recurrent GBMs and increase the length of progression-free survival compared to patients who did not use NovoTFF. The only disadvantage might be that the cap needs to be worn for 18 hours a day.  Then again, if that 18 hours a day can prolong a patient’s life, the inconvenience might be worth it.

NovoTFF has been so successful that it’s also be tested in clinical trials for pancreatic cancer, ovarian cancer, mesothelioma, and brain metastasis from lung cancer. Obviously in these cases the device has been changed so that it attaches to the torso instead of sitting on the patient’s head.  Research is also being performed by individual doctor’s  to see if NovoTFF may work for newly diagnosed GBM patients or for other kinds of cancer.

If you want to learn more about Tumor Treating fields and this fascinating new treatment, check out this Ted Talk 


What is a sunburn? Featuring Olympic Gold Medalist Misty Hyman


Misty (left) and me getting ready to swim

In this two part series, I partner with my friend, Olympic Gold Medalist Misty Hyman, winner of the women’s 200 meter butterfly in the 2000 Australian games.  Misty currently coaches private lessons, leads swim clinics, and gives motivational speeches around the world.  Misty was also recently named the senior assistant coach for the Arizona State University swim team. In her spare time, Misty extends her passion for swimming into the community as a spokesperson for FitPHX and encouraging everyone to learn how to swim.

Swimmers, as opposed to scientists, spend a lot of time outside.  Whether in the pool, by the pool, or in and around the beach, swimmers have a thing for the outdoors. With the outdoors, comes the sun.  With the sun, comes the possibility of a sunburn. And in Phoenix, where there are nearly 300 days a year with sun, a sunburn is even more likely. We all know that you should wear sunscreen to avoid getting a sunburn, but most people don’t know what a sunburn is or why you want to avoid it.  That’s what I’m going to talk about today.

sunburned_hubbySo what is sunburn? Sunburn is a response to the UV light of the sun.  The UV light is a damaging agent to DNA, the genetic code within each of your cells responsible for making your cell function properly. If there is a lot of DNA damage caused by the UV light – if you are in the sun for too long – this is a trigger for these damaged skin cells to commit suicide in a process called apoptosis. Before your cells die, this damage induces an inflammatory response, which is what causes the redness and the heat that accompany a sunburn. A few days after the sunburn, your skin starts to peel – this is the layer of skin cells that committed suicide peeling away from your body.  To summarize – sunburn is essentially a form of radiation poisoning to the skin that kills an entire layer of skin cells because the DNA was too damaged for the cells to live.


Taken by Nick Sherman and used under the Creative Commons License

Now as you and I both know, you don’t always get a sunburn when you lay in the sun (or a tanning bed, which also using UV light and has the same affect as the sun’s UV rays). Instead you could tan.  Tanning is a defense mechanism of your cells against the DNA damage caused by the sun’s UV rays.  How does it work?  The UV triggers special cells in your skin called melanocytes to redistribute or darken a pigment called melanin.  This pigment absorbs the UV light and protects the DNA from the damaging effect of UV.  If you are naturally darker skinned or already tan, the melanin absorbs the UV light so you are less likely to damage your DNA and less likely to sunburn.  But this doesn’t mean that you should just spend all of your ‘working on your tan.”  The melanin isn’t a fail safe UV protector and DNA damage still occurs.

Now that you know how sunburn and tanning works, maybe you’re thinking about how you’re out in the sun all the time, but you don’t get burned or you burn every once in a while but not all the time, so you must be okay. Maybe not.  When the UV light damages your DNA and you don’t burn, your cells still have to repair this DNA damage.  If the DNA damage isn’t repaired, you could end up with permanent mutations in the DNA of of your skin cells. These mutations may change the function of a protein and affect how your skin cells function.  Let’s say for example that you get a mutation in a gene that prevents your skin cells from dying next time they are hit with too much UV from the sun. The next time you get a sunburn, this cell will get damaged, it won’t die, and it will grow and divide with this mutation. Mutations then have the opportunity to accumulate and at a certain point will have enough mutations that the cells grow out of control and form skin cancer.

This can all be avoided in a number of ways.  You could become a scientist and never have the time to go outside because you’re always in the lab (or in my case, because your office is in the basement).  Since that likely won’t happen, you do have the option to avoid UV exposure by covering your skin with light clothing, a hat, or sunscreen.  You can also avoid spending long periods of time in the sun or limit your exposure to times of day where the UV rays are not as strong (when the UV Index is low).  Either way, the DNA mutations accumulate over a lifetime of exposure, so decreasing exposure or protecting your skin at any age will provide an added benefit and decrease your risk of skin cancer.

Misty’s Message: In the 4th grade, Misty did a science project on sunscreen and won the elementary school science fair.  Clearly, avoiding sunburn has been an interest of hers from early on.  Her advice is still the same as her science fair conclusions in the 4th grade: ” no matter what time of day it is, you should always wear your sunscreen especially when you’re in the pool.” The one exception is swimming at midnight – then you’re okay.

Why can all of your cells commit suicide?

growth-death-balanceWe’ve discussed how cells can grow and divide through the cell cycle and a process called mitosis.  Equally as important to cells growing and dividing is the ability of cells to die.  Why do cells have to die? During human development cell death is necessary.  For example, in the womb fingers and toes are attached to one another by a webbing made of cells.  During development, these cells die so that your fingers and toes are separate. A great non-human example of cells dying during development is the tadpoleDevmetamorphosis of a tadpole into a frog.  The cells of the tadpole tail die to make a mature frog that does not have a tail.  As an adult, your hair, skin, gut and other cells constantly divide.  In fact ~ 60 billion cells are made each day. Imagine if cells didn’t also die each day – you’d be ENORMOUS!

This cell suicide is called apoptosis (pronounced a-pah-toe-sis) after the Greek meaning “dropping off ” or ” falling off ” of petals from flowers, or leaves from tree.  Apoptosis is  a mechanism that every single cell in your body has to commit suicide.  Why in the world would this mechanism exist? In part, it exists for the reasons mentioned above – to remove unneeded tissue during development or to balance out cell growth.  But apoptosis also provides a fail safe for cells to remove themselves if they become damaged so that they don’t damage the rest of the organism.

apoptosisSo how does apoptosis work?  Obviously your cells don’t just kill themselves willy nilly.  The cell must receive a trigger the initiates the process.  These triggers can either come from inside or outside the cell.  For example, UV light from outside of the cell can trigger damage to the DNA.  If this damage isn’t repaired, it will start the process of apoptosis.  As another example, when cancer cells are treated with chemotherapy, this often damages the DNA or messes with the cell cycle so much that it triggers apoptosis.  Once triggered, proteins are activated that act like protein scissors, cutting up proteins and DNA inside the cell.  This does a few things: it shuts down activity within a cell and makes the pieces of the cell smaller so that they can be packaged up and thrown away.  It’s like a kitchen demo (or any kind of demolition)  – you knock down the cabinets with a sledgehammer so that they don’t work to hold your dishes anymore and then break them into small enough pieces that they can easily be thrown in the dumpster.  Once cell pieces are broken down, the cell  packages up the contents (called blebs – see picture at right) and blebbingthese blebs are eaten (actually, they are absorbed…but “eating blebs” is more fun to say) by neighboring cells.  What’s so awesome about this process is that no trace of the cell is left.  It’s a clean suicide that leaves no trace of the body behind.  Why is this important?  We can compare apoptosis to another type of cell death called necrosis.  If you cut your arm, cells die by necrosis and they spill their contents everywhere.  When this happens, your arm can get inflamed and this inflammatory reaction can be bad for you.  During apoptosis, since everything is cleaned up nice and neat, there is no inflammation and the body can just move along as if nothing happened.

apoptosis_diseaseNow what if the trigger is defective or the machinery is broken and cells don’t die when they are supposed to?  This is one of the causes of cancer.  Of course cancer is a result of too many cells, but this can either be from cells growing too fast OR from cells not dying when they are supposed to OR a combination of both.  On the other hand, what if too many cells die when they aren’t supposed to?  This can cause the neurodegeneration found in Alzheimer’s disease or the loss of immune cells in HIV/AIDS infection.  Therefore, understanding apoptosis and the exact way that cells die can help scientists to induce cell suicide (e.g., to kill cancer cells) or prevent it when needed.