Thursday, 2 August 2012

The big cure for the big ‘C’

This time I'm not going to make any promises. I'm going to try and keep this place going better than I have done but I may get distracted again. There's a lot of fun stuff ahead, but it should mean you'll get to see me cropping up in other places very soon. In other news, if you didn't see it, I got a post on the network on Monday which I'm very excited about. It's on the theme of new beginnings and organising my first conference.

I'd also like to say a quick hello to some of my readers that I've had the good fortune to meet around Cambridge since I last posted anything. I'm always surprised that people have actually heard of my ramblings and am glad that I'm not talking to myself here (although after so much inactivity that may have changed :S )

Anyway, people are always asking me if I've cured cancer yet. This is one of the things that my lab and many others are working towards, in a roundabout sense. But it seems likely that there will never be one cure for all cancer and here's why:

At the risk of being cliché, given all the recent media activity (which I have spectacularly missed the opportunity to write about), finding the ‘cure for cancer’ is to biology what the Higgs Boson was to particle physics. Everyone’s working on it and it means a lot – not just to our understanding of the universe, but to human healthcare – and it may not even exist.

People like to think there can be a simple pill that will fix any problem in life from cancer to cellulite, obesity to osteoarthritis (source).

It’s very nice and easy to think of one simple, easy to administer cure – this is the ultimate dream for many illnesses – but most diseases just aren’t that simple, in particular a ‘cure for cancer’ is a very misleading concept.  It suggests that cancer is one illness that is the same every time it occurs and therefore should have the same solution each time. Actually, there are probably as many cancers as there are people with cancer, with each one unique and different to any other, to some extent.

We already know that almost everyone has a unique set of genes (unless you’re an identical twin, or a clone), so every cancer has an individual starting point, add to this any number of thousands of possible genetic errors that can result in cancer and it’s easy to see how each cancer is special.

Cancer is a genetic illness, it happens when something goes wrong in your cells that changes your genetic code (stored as DNA) which changes how your genes work. Every cell in your body has a copy of all of your genes and they are carefully controlled to ensure that each cell works properly as part of your body. You are not born with cancer (although your genes can make you more likely to develop it), at some point in your life something happens to one of your cells that starts a new cancer.

Damage to the DNA that stores genetic information can ususally be repaired.

Usually, if an error occurs in the genes in one of your cells it will be repaired or the cell will die. Mistakes can occur in genes as a result of many different factors, including some infections or exposure to certain things such as tobacco smoke or UV radiation from sunlight but sometimes they just happen as a natural part of life. In a relatively small number of cases the genetic error allows a cell to evade death and continue living with a genetic code that has mistakes in it, these cells are often called immortal cells. Because immortal cells don’t die when they are supposed to they tend to gain more and more errors in their genes, and these errors become progressively larger and more damaging.

Eventually the genes of an immortal cell can become so altered that the cell starts to growing rapidly and make lots of copies of itself. This forms a tumour, which is a large lump of genetically altered cells. The problem is that, although these cells have acquired many mistakes, they are still fundamentally the same as the cells in the rest of the body, so it is very difficult to tell the difference between a cancer cell and a healthy cell and it is very difficult to kill cancer cells without affecting other normal cells.

Images of the chromosomes (DNA pieces carrying genes) from a cancer cell. In a normal cell each chromosome would be only one colour. This image shows how parts of different normal chromosomes have rearranged and fused together to make new scrambled chromosomes carrying scrambled genes. (source) NB: Not all cancer genomes are this signficantly altered.
In addition, the ability for cells to grow and copy themselves is very important and is very tightly controlled, meaning that there are lots of genes that have an effect on cell growth. This also means that mistakes in any of these genes may contribute to cancer (genes that can contribute to cancer are called oncogenes). This complicated system means that several mistakes are generally needed for cancer to occur, meaning that cancer is relatively unlikely to occur (On average one in three people will develop cancer, that’s one cell out of tens of billions of cells, which is actually pretty rare). However, it also means that many genes can contribute to cancer, meaning that cancers are not the same as each other.

This is why it’s difficult to find a cure, and why a cure for all cancers may be impossible. It would be much like finding a cure for all the different types of flu or the elusive cure for the common cold (which is actually estimated to be over 200 different illnesses, each time you get a cold it’s different to all of the ones you’ve had before). Additionally, because so many genes are involved and so many different cancers exist, it is very difficult to study cancer as a whole, and not just one specific example.

The only common factor in all cancers is that they cause uncontrollable growth of immortalised cells. Current chemotherapy methods use this by killing cells that grow rapidly, but there are other cells in your body that grow quickly too, these also get killed and this is what causes the severe side-effects of cancer treatments. Many other methods have been suggested to target growing cells, but all would probably have similarly unpleasant consequences. The surgical alternative physically removes the cancer cells, but this is often impossible – due to complexity or location – and even one remaining cell is enough for a relapse, hence intensive radiotherapy or chemotherapy is still needed.

A collection of known chemotherapy drugs. This aggressive collection of chemicals is very good at killing rapidly growing cells (source).
A few approaches have been thought of that, with further research, may be useful in treating most cancers, but even these will not be 100% effective. A primary target is the blood supply to a tumour – rapid growth requires plenty of supplies. Successful tumours are able to encourage the growth of new blood vessels to keep them well supplied with nutrients and oxygen, without this many of the cells rapidly die and a tumour can generally only reach a certain size. Preventing blood vessel growth may be a great way to stop tumours advancing, and has minimal effect on normal tissues. However, not all tumours are dependent upon plentiful blood supply, or they may already have access to one.

There are also key regulators of cell growth, genes at the centre of a complex system of control. These have a lot of potential but they are generally of great importance to all of our cells and so a lot of careful research is needed to understand exactly how they work before we try targeting them for cancer treatments. Some of these genes have significant roles in a large number of cancers in specific parts of the body, but always occur in a low number of all cancers, so targeting them is only effective for some patients.

The cancer enigma was one of the driving forces behind the inception of ‘bespoke medicines’, which use information about your genetics to design a treatment regime that is specific to you and offers the best chance of recovery. In the future, it should be possible to study how a cancer differs from the person with cancer and use this to select drugs that can target the tumour more specifically, so has fewer side-effects and higher success.

In the near future doctors could use your genetic code, and the genetics of specific tumours to assess the best possible treatments to use, with the highest survival and fewest side-effects (source).
When it comes to the cure for cancer, the simple answer is that there is no cure. Cancer is simply too variable, too inconsistent and too complex to have one solution that will work for almost all patients. Instead the focus is now on understanding each cancer on an individual level so that the best possible treatments can be selected to give the best chance of recovery for each patient. In the age of genomics, as it becomes ever cheaper and easier to acquire a patient’s genetic code, it is becoming possible to treat everyone as the unique individual they are rather than applying universal treatments that may or may not be very effective and hoping for the best.

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