Bullseye!

There’s one thing that everybody knows about cancer treatment.  Whether you have suffered from the disease yourself, or if you’ve ever known anyone that has, you will know this one thing.  And it is that current cancer treatments produce really nasty side effects.

Both radiotherapy and chemo can be really tough for the patient (especially chemo).  The most commonly used forms of treatment can cause extreme exhaustion, nausea & vomiting and suppression of the immune system, which can result in an increased risk of severe (and potentially dangerous infections).  So, the question this post will try and answer is why.  Why are these side effects so common?  What causes them?  And can they be prevented?

Now, part of the problem is in how these treatments work.  With radiotherapy, the radiation beam has to pass through your body to get to the tumour.  This means that it will be going though normal tissue and causing damage before it hits the tumour.  There are ways to try and minimise this.  You can use multiple beams at lower intensity, which came from different directions and are all focused at the same point.  This means that, for each individual beam, the dose that passes though the normal tissue is reduced.  But, as all of the lower dose beams are focused on the tumour, the overall dose that that the tumour gets is much higher.  But, unfortunately, while you can reduce side-effects by doing this, you can’t remove them altogether, because the radiation still has to hit the tumour, so still has to go through your body to get there.  And this will, inevitably, cause damage to the normal tissue it goes through and this, in turn causes side-effects.

In the case of chemotherapy, it’s even trickier.  If you remember back to No Bootees, you’ll remember that I explained that cancer is caused by an imbalance of growth signals inside cells (which I called Go! signals).  Now, the way that chemotherapy drugs work, is to target the effects of these imbalances.  They either target the Go! signals directly, or they target the consequences, ie. the rapid cell growth & division.

But the problem is, while cancer is caused by these Go! signals, the signals themselves are not specific to cancer cells.  Normal cells use them as well. And any normal cells which use Go! signals that are the targets of chemotherapy drugs will also get damaged.  Not only that, but cancer cells are also not the only cell types that grow and divide rapidly. Other, (normal) cell types do this too and are also susceptible to chemotherapy drugs. Among the normal cells that can be damaged, and thus cause common  side-effects, are those which belong to your digestive and immune systems.  This is why vomiting and other digestive problems are frequently found in patients getting chemo.  As is a compromised immune system, and this can lead to secondary infections, which the patients are unable to fight off until the treatment stops and their immune systems recover.

So these are the reasons why side-effects happen.  Now, obviously, the ideal thing would be to try and get rid of them, while keeping the anti-tumour effects.  That’s the Holy Grail of cancer therapy.  And that is what a lot of research is trying to achieve.  The ultimate aim is to target all, or at least as much of, the treatment to the specific spot where the tumour is in order to avoid the side-effects caused by hitting normal tissues.  Or, if you’ll pardon the analogy, if you think of your body like a dartboard with the tumour in the middle, we want to try and make all of the anti-cancer darts that we throw hit the bullseye, and only the bullseye.

In the case of radiotherapy, the biggest advances have involved improvements in scanning techniques.  Basically, the more accurately the doctors can locate the tumour, the more accurately they can focus the radiation beams and, consequently, the lower the risk of unintentional collateral damage.  The invention of CT scanning was a big improvement over X-rays.  And the development of MRI was an even bigger advance.  All of these improvements in scanning technology have helped to minimise the amount of radiation that hits normal tissue, thus minimising, as much as possible, off-target side-effects.

In the case of chemotherapy, it gets a little trickier.  As I said, the Go! signals that are responsible for cancer growth are not specific to tumours, so a lot of the research into developing new chemo drugs has gone into trying to pick apart the way that the signalling works inside the cells, to try and isolate the parts of the network that are only found in cancers, and develop new treatments based around the markers that are truly tumour-specific .

Other studies try to see if there are patterns of Go! signals that are more commonly found in tumours.  For example, maybe signal A is only found in the immune system and signal B is only found in the digestive system.  So, if you only use a high dose of anti-A chemo, you’ll get tumour and immune cell death and if you only use a high dose of anti-B chemo, you’ll get tumour and digestive system cell death.  But, both A and B are found in cancer cells.  So, anti-A and anti-B in combination, you could use lower doses of each.  This would mean that you’d obviously get lower drug doses in the normal tissues and therefore less collateral damage.  But it would also mean that giving the anti-A + anti-B drugs together would result in a higher chemo dose in the cancer than in either of the normal tissues, leading to greater tumour toxicity.  So, more of the darts hit the bullseye and fewer hit the other numbers.

And that’s what research into new and improved therapies will strive for.  To try and get to the situation where many, many darts can be thrown at once and all of them hit the bullseye.  It won’t be easy – it isn’t easy –  but we’ll keep on trying.

ResearchBlogging.org

AG McCluskey (2015). Bullseye! Zongo’s Cancer Diaries