day 22 dancing with my new friend taxol

Yesterday was my second chemo, and like the second time you do anything, was different from the first. It wasn’t all new, and yet it hasn’t exactly become routine either. It was a little odd. I am just at the three week mark, and it had been a flurry of activity with tests, doctors visits and new information almost daily for the first two. Last week I managed to have at least one medical appointment every day, not bad for a person who doesn’t typically see a doctor more than once every few years. But this week it has been much calmer, and it has been hard at times to remember that I am a cancer patient. I realize that pretty soon that won’t be so hard anymore, as chemo asserts itself both on my tumor and with side effects, but at the moment, as I go through my work day, you can sort of forget. And that is not all bad. 

After my pre-chemo blood draw to check blood counts I went back to meetings, and completely forgot to apply the lidocaine creme to my port an hour before it was going to be accessed for taxol. Luckily my wife texted me to remind me, and I got it on there in good time. Then when I got to my office to drop by work papers and head over to the clinic, I realized I had forgotten my little hospital bag at home, with headphones, book, hat etc. Not a tragedy, sure, but another sign that I haven’t quite gotten into a routine yet. Hmmm. Must remember. 

Off to the main building ambulatory care center – very nice, with a private room and very attentive staff. All went well, and for me came with a sensation of non-eventness. Sure, I could see the IV bags emptying, and was shown the meds and all, but it was hard to see a before and after. I was trying to visualize the drug going into my blood, heading over to the tumor and giving it a good kicking. I was thinking about taxol, and cheering it on.

So what is taxol doing anyway (http://en.wikipedia.org/wiki/Paclitaxel)? What it does is interrupt microtubules – these are part of the cytoskeleton, or the skeleton of the cell if you like. Microtubules are like little columns that extend throughout the cell, and are used in a normal, resting cell to give it shape, structure, motility and to move stuff around. Other proteins actually walk along the microtubules and drag cargo behind them. You can see animations of what this looks like on YouTube ( or see the actual microscopy of this in an experimental system ). This is very important to get large things, like organelles, moved around, and if you consider that some of your nerve cells can be 1.5m or nearly 5 ft long in humans (what about giraffes or whales…) this machinery is pretty important. 

Another critical function of the microtubules is during cell division. When you take a cell and want to make two of it, you have duplicate its components, and share them equally. When it comes to DNA it is particularly critical that pretty much every time this happens with complete accuracy, so that each daughter cell gets exactly one copy of each chromosome. You need a mechanism that drags half the chromosomes to one end of the cell, and other half to the other. The machinery that does this is called the spindle, and its main structure is made of microtubules. The best way to understand what happens is to watch a quick video. Microtubules are called fibers in this one: 

At the core of microtubule function is their rapid, regulated assembly and disassembly. For example as the cell changes shape, or more importantly here, as it divides, it has to breakdown and rebuild the microtubules all the time. A great example is the mitotic spindle you just saw in the last video – it is only needed for a relatively short time as the chromosomes are assembled and pulled apart during mitosis. In fact the whole process of mitosis takes only 10% of the cell cycle. A very rapidly dividing cell, such as you have in tumors, might have a cell cycle of 24 hours, meaning that it divides into two cells once a day. So it would be in mitosis less than 3 hours, and the assembly of the spindle might only take about 20 minutes. But it is absolutely critical to have it at that time.

So what does taxol do? It actually prevents microtubules from disassembling. Why does that stop the cell from dividing? Because the cell does not assemble the mitotic spindle with brand new microtubule building blocks, but rather it disassembles the cells existing microtubules and reassembles them into the spindle. So by preventing the cell from temporarily repurposing the microtubules, it allows normal stuff to go on (this is important, as many cells are using their microtubules to have the right shape and move stuff around) but prevents the cells that happen to be trying to divide at the time you get the drug from doing so. And when they get stuck in this phase for too long, it causes them to die. (Interestingly, there are also drugs that do the opposite: stop microtubules from assembling – for further reading look at colchicine. They are not very useful in cancer treatment as they are too toxic.)

That also explains a few other things you might be thinking about. Why do I have to have so many treatments and over such a long period of time? Well there are two things to think about. There are of course lots of cells in the body that divide in the course of normal function. They are in tissues that are continuously replaced: skin, hair, gut, immune system etc and they are also affected by the drug. So the key is to give chemo in a way that harms the tumor enough, and doesn’t harm the normal cells too much. This is called the therapeutic window or index – the larger, the more doses and regimens there are where you get enough effect and not too much side effect. The other consideration is that cells in the tumor are dividing totally asynchronously, and not even all the time. So the taxol I got yesterday, which will be active in my body for about 12 hours (half life of around 6 hours) won’t even have a chance to get all my tumor cells. When you think of dividing cancer cells don’t think square dance. Think rave. So I’m hoping that the cancer cells that were taking a break yesterday while we were handing out the taxol, will be back in the mosh pit next week. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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