Professor Gerard Evan, University of California San Francisco
Part of the show How Cancers Form, Cancer Biology and Future Therapies
Chris - We've devoted tonight's show to the subject of cancer. Lots of people know about cancer because one in three people die of it, but they don't tend to know what it is. So what actually is a cancer?
Gerard - Cancer's probably the best example we've got of evolution in action. Cancer's what happens when cells manage to throw off the shackles that normally restrain them and start to expand. As they expand they evolve and they get worse and worse and eventually people die.
Chris - But why is it that it's so common as a condition and why hasn't the body evolved not to develop cancer?
Gerard - Well the first thing is that it's not that common. Although one in three people get it, cancers arise from single cells and the average human body contains about a hundred thousand million cells, any one of which in principle could become a cancer cell. So in fact, cancers occur in one in a hundred thousand million times in one in three individuals in seventy years, which is very very rare. The reason so many people get cancer is that there are so many cells and you live so long. Really, cancer is suppressed and we have lots of mechanisms to suppress cancer being evolved, but like all evolutionary selection, it only works until we get to reproductive age. Once we've gone beyond reproductive age, evolution doesn't care.
Chris - You say that though but grandmothers have an important role too. I know this because I've recently acquired a new addition to my family and I can tell you that grandmothers are actually quite handy, so there must be some degree of evolutionary pressure to keep grandmothers in the family.
Gerard - Yes it's absolutely true and I've thought about this as well. So maybe in millennia to come humans will get less and less cancer because they'll be selected out as we want granny around. But we're so close to other organisms that don't live very long, and for them the grandparent generation is pretty much irrelevant in terms of care-giving.
Chris - Let's look at why you get cancer though, because it's fair to say that it's a genetic disease, and we're going to be hearing about one of them from Kat Arney who's at the Cancer Research conference this week about a new gene for breast cancer. But why should genes cause cancer? What are the mechanisms involved? What's going on?
Gerard - The thing we have to appreciate is that cancer cells aren't doing anything that normal cells don't usually do. So every time you cut your finger, cells proliferate very rapidly, they generate a blood supply, they recruit other tissues, they rebuild and remodel and mend the cut in the finger. So you have all the machinery you need to become a tumour cell. The point is that it's very guarded and reigned in in normal cells. Cancer is a disease when the mechanisms for reigning in those processes get lost or eroded.
Chris - How does that happen?
Gerard - It happens through mutation and through cosmic rays and various nice things that you eat and who knows what.
Chris - Well even the air that we breath because oxygen causes cancer.
Gerard - That's right. We live in this nasty gas second only to chlorine for how viscous it is, but we've evolved to cope with it. But as I've said, we've evolved to cope with it to a reproductive age and no more.
Chris - We're protected from cancer up to a certain age and we have repair mechanisms to stop the damage from happening. How do they actually work?
Gerard - That's a bit of a mystery actually because as I've said, cancer cells are really only doing what normal cells are doing. You've got all these mechanisms that prevent cancer but how do they tell what's a cancer cell and what's a normal cell. This is actually a deep mystery and we don't really understand that. What we do understand though is when the DNA in the cell gets damaged, there are immediate repair mechanisms that come in and fix the damage - at least as best they can. The problem is that sometimes they make mistakes and that's when you get a mutation. So in some ways you could say that mending the damage is what causes the cancer because that's what's causing the mutations. We also have another response to DNA damage in many cells which is to just trash the cell. That's actually the best way of preventing cancer, but unfortunately if you did that every time you wouldn't have a body left.
Chris - So when we actually have a look at what's going on in a cell, can you just talk us through how a cancer begins? You don't just wake up one morning and have cancer. It obviously has to evolve from somewhere and changes have to accrue. How does that process happen?
Gerard - The clinical disease, of course, is the end point of a whole variety of processes by which time the individual cell that caused the cancer has multiplied and grown and started to erode your normal tissues. The initial events which cause cancer arise in individual cells and they probably happen thousands of times a day, but they never get very far because we have these powerful mechanisms that put the breaks on incipient cancer cells and stop them dividing very early on or kill them.
Chris - What about spread around the body?
Gerard - Why do cancer cells spread around the body? Well a lot of cancers don't, but the ones that bother us do. So the point is that cancers start in one particular site, and they erode the tissue around that site, and if they stay put they're an operable cancer. They're not the things we usually worry about. If they start to break loose and wander round the body and colonise elsewhere, just basically acting like and independent life form, that's when we have the problems.
Chris - You published a paper recently where you had some very interesting things to say about how we might be able to make chemotherapy and radiotherapy a bit more comfortable for people in future. How does that work?
Gerard - I think it goes back to why we aren't able to cure cancers. The truth is, we can kill any cancer that any person has ever had; we just can't keep the patient alive at the same time. We don't have drugs that are sufficiently good at discriminating between the normal cells and the tumour cells. One of the reasons for that is that many normal tissues in the body turn over very rapidly and they're just as sensitive to the cancer treatments as are the cancer cells, and sometimes even more sensitive. If we could preserve those normal tissues and turn down their terrible responses, then we could deliver higher doses of radiotherapy and chemotherapy to the tumour cells and probably kill more cancers. The work that we did recently was looking at what the relationship is between the mechanisms in cells that respond to damage to the DNA, and whether those are the same mechanisms that are widely thought as the mechanisms that prevent tumours occurring in the first place. The idea being that if you have a mechanism that responds to DNA damage by killing the cell, then it prevents it from accumulating mutations and becoming a tumour cell. But our data seem to indicate that the two are actually separate and very different, and you can dispense with the nasty bit, the DNA damage response that kills off all sorts of normal cells, and still retain the tumour repressor functions of this particular protein; a protein called p53.