Will we ever win the "war on cancer"? The latest figures show just how distant a prospect victory is right now. In the US, the lifetime risk of dev
Will we ever win the “war on cancer”?
The latest figures show just how distant a prospect victory is right now. In the US, the lifetime risk of developing cancer is 42% in men and 38% in women, according to the American Cancer Society. The figures are even worse in the UK. According to Cancer Research UK, 54% of men and 48% of women will get cancer at some point in their lives.
And cases are on the rise. As of 2015 there are 2.5 million people in the UK living with the disease, according to Macmillan Cancer Support. This is an increase of 3% each year, or 400,000 extra cases in five years.
Cancer is not only extremely pervasive, but also becoming more and more common
Figures like this show that cancer is not only extremely pervasive, but also becoming more and more common. But why will so many people develop the disease at some point in their lives?
To get to the answer, we must understand that cancer is an unfortunate by-product of the way evolution works. Large and complicated animals like humans are vulnerable to cancer precisely because they are large and complicated.
But even though it is evolutionary processes that have made cancer such a problem, it is also evolutionary thinking that is now leading to pioneering treatments that could stack the odds against cancer and in favour of our health.
To understand how cancer exists at all, we need to go back to a fundamental process that occurs in our bodies: cell division.
A cancerous cell breaks all the rules of controlled division that our other cells follow
We each started out when an egg and sperm cell met and fused. Within a few days, that egg and sperm had turned into a ball containing a few hundred cells. By the time we reach adulthood about 18 years later, those cells have divided so many more times that scientists cannot agree, even to the nearest few trillion, exactly how many cells our bodies contain.
Cell division in our bodies is very heavily controlled. For instance, when you were first growing your hands, some cells went through “cell suicide” – a process called apoptosis – to carve out the spaces between your fingers.
Cancer is also all about cell division, but with one important difference. A cancerous cell breaks all the rules of controlled division that our other cells follow.
“It is like they are a different organism,” says developmental biologist Timothy Weil of the University of Cambridge in the UK. “The better that cell gets at dividing faster than its neighbours and gaining nutrients, the more successful it will be as a cancer, and the more likely it will survive and grow.”
Healthy cell division is marked by control and restraint, but cancerous cell division is wild, uncontrolled proliferation.
“Adult cells are constantly under strict control,” Weil says. “Basically cancer is a loss of control of those cells.”
Cancer can only grow in this uncontrolled fashion if some of the genes that usually stop any accidental cell growth – such as the p53 gene – get mutated in the cancer cells.
If just a few survive they have the potential to rapidly multiply again and regrow the tumour
However, our bodies are pretty good at spotting these mutations. There are biological systems within us that step in to destroy most mutated cells before they can cause us harm.
We have several “corrective” genes which send instructions to kill any corrupted cells. “There’s millions of years of evolution that’s gone into this,” says Charles Swanton of the Francis Crick Institute in the UK. “It’s pretty good but it’s not quite perfect.”
The threat comes from the tiny number of corrupt cells that do not get fixed. Over time, one of these cells can grow and divide into thousands, then tens of thousands of cancer cells. Eventually there may even be billions of cells in a tumour.
This leads to a truly challenging problem. Once that initial corrupt cell has divided and multiplied into a tumour, a person will have cancer until every single one of the cancer cells has been obliterated. If just a few survive, they can rapidly multiply and regrow the tumour.
Cancer cells are not all alike: far from it. Whenever a cancerous cell divides, it has the potential to pick up new mutations that affect its behaviour. In other words, they evolve.
No two cancer cells in a tumour are the same
As the cells inside a tumour mutate, they become ever more genetically diverse. Then evolution goes to work to find the most cancerous ones.
Genetic diversity is “the spice of life, it’s the substrate upon which natural selection acts”, says Swanton. By this he means evolution by natural selection, first proposed by Charles Darwin in 1859.
Just like individual species – humans, lions, frogs, even bacteria – gain genetic variation over time, so too do cancer cells. “Tumours don’t evolve in a linear manner,” says Swanton. “They evolve in a branched evolutionary manner, which means that no two cells in a tumour are the same.”
In effect, the cells of a tumour are evolving to become more cancerous. “Essentially we are dealing with branches of evolution that create diversity and that create fitness, and allow cell populations to survive therapy and ultimately outwit the clinician,” says Swanton.
The fact that tumours are constantly changing their genetic makeup is one of the reasons why cancers are so hard to “kill”.
It is for this reason that Swanton, and others in the field, take an evolutionary approach to tackling cancer. Swanton, who specialises in lung cancer, is both a clinician and a research scientist. His work has revealed something that he hopes will help create effective, targeted treatment.
Think of the evolution that goes on inside a cancer tumour as like a tree with many branches
Think of the evolution that goes on inside a cancer tumour as like a tree with many branches. At the base of the tree are the original mutations that triggered the tumour in the first place: mutations that should be shared by all of the cancer cells in the tumour.
In theory, a therapy that targets one of those base mutations should destroy every cell in the tumour. This is an approach that some therapies already use. For instance a drug called EGFR therapy targets lung cancer, and a BRAF inhibitor protein attacks the faulty gene which can lead to melanoma.
The trouble is, these therapies do not work as well as we might hope. Even in these targeted therapies, resistance often appears over time.
“It occurs because there will be one or more cells in the tumour branches that has a resistance mutation that allows it to outwit the therapy,” Swanton says.
In other words, some of the branches of the cancer tree have evolved in a way that makes them less vulnerable to attack through the base mutation. They can dodge the therapy.