Following on from my post on the new treatment for ALL, I thought I’d go into cancer in general a bit more. In this first part of a double post, I’ll briefly go into what cancer is and the principles of the main types of current treatments. In the second part, I’ll consider some of the more futuristic cancer treatments that are starting to enter the mainstream.
How cancer happens
Cells become cancerous when they acquire a random mutation in their DNA that makes them divide and make new cells. Every time a cell divides it has to copy all its DNA, so tissues in which cells normally divide quite a lot are therefore quite prone to acquiring mutations simply as a matter of probability. This is why some cancers like bowel cancer, skin cancer and breast cancer are more common than others in which cells do not divide often (like brain). Normally, cell division is very strictly controlled so that cells only do it when they’re supposed to, but over a lifetime, errors can creep into the copying process or into the detect and repair mechanisms that exist to try and minimise this (there are millions of DNA “letters” that need to be copied precisely!). These mutations tend to occur in certain sets of typical genes that are involved in the control of cell division and DNA copying and repair. So you get mutations in:
- Genes that tell cells when to divide – either ones that say “divide now” get turned on when they shouldn’t, or ones that say “don’t divide” get turned off
- Genes that detect DNA damage that the cell cannot repair. As a failsafe, if a cell cannot repair damaged DNA, it should self-destruct (referred to as programmed cell death, or apoptosis, because it’s done in a controlled way as opposed to the cell just messily dying). Sometimes the self-destruct genes get turned off.
Later, if a cancer spreads, you get different types of mutation involved in cell movement that makes them break out of their original site and allows them to move into other parts of the body where normally the environment would not be favourable for their growth.
Usually you will need more than one mutation to make a cell cancerous, but once it begins to divide uncontrollably, you increase the chance of more mutations occurring. There is a natural selection process in that if you have a group of cancer cells dividing, and one gets a new mutation that makes it divide faster, it will out-compete the others until most of the cells in the tumour have the new mutation. Similarly, if you get a mutation that allows the cancer to spread to other sites in the body (metastasise), these cells again have an “advantage.” This is of more than academic interest because this is one reason why treatments often work for a while and then stop working. Another reason is that, like bacteria, tumour cells can evolve resistance to drugs, via a similar process. Unfortunately, one of the problems with cancer treatment is that you very rarely manage to kill every single cell in the tumour, and any few that survive again are undergoing this selection process which means they tend to get new mutations which makes them harder to kill.
Principles for treating cancer
The main difficulty with treating any type of cancer is that it is the body’s own cells that you need to get rid of, instead of foreign invaders like bacteria and viruses. This means that it is very hard for the immune system to recognise these cells as dangerous (but not impossible – cells called T-cells are important for this; they are good at recognising your own cells when they are infected with viruses, for example). Traditional chemotherapy exploit the very molecular defects that make cells cancerous in the first place: the mutations that lead them to divide uncontrollably, or spread where they shouldn’t. Generally, it tends to affect cells that are dividing and making new cells very quickly; this is a characteristic of cancerous cells, which are dividing improperly and making the tumour grow. Ordinary cells are able to pause and repair their DNA, but cancer cells have lost control of the cell cycle, so they don’t do this, eventually causing so much damage that they die. It is also why you tend to get lots of side effects; there are cells in your body that naturally have a high turnover and divide frequently, e.g. the ones lining your gut, which also get affected. Radiation therapy works on the same principle – ionising radiation damages DNA, which dividing cells are copying as they make new cells, and so they are more vulnerable to it, and, again, cancer cells are not usually able to stop and repair their DNA.
I think people often don’t realise that there has actually been huge success in both diagnosing and treating cancer over the past few decades. Overall survival has more than doubled in the past forty years. If you want to look at some statistics, you can find a very wordy factsheet here, or, for an easier-on-the-eye website where you can pick and choose a bit, here:
Nevertheless, cancer is still a diagnosis that we all dread, and with good reason. Probably this is because it still affects a lot of people – more so, as the population is aging (this is simply a matter of probability: as you get older, your cells will have been through more rounds of division, and so are more likely to acquire a cancerous mutation, in addition to the fact that the body becomes less able to maintain itself). And the fact remains that it is difficult to cure, with often gruelling treatment regimes, and a risk of recurrence. Cancer is not just one disease; it is a myriad of diseases with a common underlying cause: breast cancer is a different beast from lymphoma. But it is also true that no two breast cancers are the same; not only can they be divided into different types, but from one person to the next, the mutations that have caused the cancer (and in particular, those that cause it to become more aggressive and invasive once it is established), vary. So what is the future of cancer treatment? Is it this “personalised medicine” we’ve all been hearing about?
I’ll be posting some strategies for new cancer treatments and examples of these in the second part of this post soon.