What causes cancer to develop?

Fran Balkwill and Andrew Wyllie discuss what causes cancer...

Fran - I'm interested in cancer and how it links with other things in the body, like inflammation. I'm also really interested in the fact that cancers aren't just made from cancer cells, but are made from some normal cells that help the cancer cells grow and spread.

Andrew - I'm interested in the way cells die. It turns out that they have to do this to be good citizens in the tissues they make up. You can think of a cancer cell as an un-dead cell; a cell that has failed to die when there's something seriously wrong with it.

Kat - What is cancer?

Andrew - It's a disease in which the internal programmes that tell a cell what to do, where it ought to be, what it should be secreting, and whether it should be moving or not go awry. This means that the cells get the wrong internal messages. The programmes are driven by genes. The genes are altered in cancer cells by a process we call mutation. In general, you need several mutations to add together to get the disordered behaviour we recognise as cancer.

Kat - Then what happens?

Andrew - It does a number of things. The most obvious is that it loses its ability to top growing and dividing. That means that you get clusters of cells that shouldn't be there at all. It also starts to break down the normal barriers that surround tissues. It starts to digest these connective tissues and move into the blood vessels that are surrounding it. It has the ability to call in blood vessels to bring in extra blood supply. In this way, the cancer manages to stoke its own fires. Sometimes the cancer cells managed to jump into the blood vessels and get circulated around the body. A small proportion of these can lodge elsewhere in the body and start growing in sites where they shouldn't be.

One last thing is that they also fail to respond normally to injury. The normal damage cells are exposed to is curiously caused by oxygen; the oxygen needed to drive the cells in the first place. Oxygen is a reactive molecule and it sometimes damages DNA. Cells have a very good way of either repairing that DNA or, for reasons we don't quite understand, it destroys itself. This process of throwing out damaged cells is a very significant part of the life of good tissues. So death is part of life. If you don't throw the cells away, you get persistence and growth of bad cells.

Kat - Fran, can you tell us some more about how the body responds to a cancer?

Fran - Andrew has just talked about cancer as a rogue cell, but in many ways, cancer is a rogue organ. It is full of the cells that Andrew has described, but in order to grow and spread, those cells bring in other quite normal cells. If you have a cut, a lot of cells come in to try and repair the damage. Similar cells are found in a cancer, but in this case, all these extra cells help the cancer to grow and spread. The process of inflammation is a very good thing in the body as it helps to fight injury and resolve the problem. In the case of cancer, the problem doesn't resolve and the cells that came in to help are all part of stoking the fire for the cancer. If the genetic damage to a cell is the match that starts the fire, this chronic inflammatory response feeds the flames. As many as half the cells ina cancerous lump will be normal cells.

Andrew - So if we had ways of interrupting that process, could we stop the progress of the tumour?

Fran - Yes, that's what we hope. Every year in this country around 220 000 people are diagnosed with cancer. Although many are cured, a very large number actually die. There are many drugs that are good at getting rid of cancer cells and surgeons are very good at getting rid of the lumps. What we find more difficult is to stop it coming back and stop it spreading. The approach of tackling the normal cells and blocking the messages that go between these cells and the cancer may be a complementary way of augmenting the very good treatments we already have.

Kat - So you're trying to find a way to harness the body's natural processes and shut them off?

Fran - Yes. One specific thing we are looking at in my lab is a series of drugs that block a molecule called TNF. Anti-TNF drugs are used for arthritis and Crohn's disease. They are anti-inflammatory drugs, and we are now doing clinical trials with them on cancer. It's the spreading of cancer that kills, not necessarily the cancer itself. If you can keep cancer under control for a long period of time, people can have a good quality of life.

Mandy - Are there any good cancer cells? Or is it just by the word cancer that it is automatically saying this is bad news?

Andrew - That's a very interesting question with about half a dozen different answers. I will offer one or two. There are cells which have lost control but haven't yet acquired the ability to burrow through the connective tissue or to spread. We call these benign tumours. Some of these have the capacity to grow into benign tumours, but in general they don't. This is why screening is so important because it gives us the opportunity to find these tumours while they are still benign. They can then be removed.

Mandy - It also gives us the opportunity for lifestyle changes like giving up smoking.