We are constantly reminded of the looming, ominous and terrible prospect of cancer. Just sitting on the underground you are surrounded by cancer propaganda – ever reminding us to be watchful of our bodies, to know the signs. But also gently reminding us that cancer research is on-going, expensive and necessary. One in three of us will die of cancer, but how many of us can honestly say that we even know what it is?
What causes cancer?
Cancer is caused by the unregulated growth of cells. Cancer cells have an unusual karyotype; that is, they have the wrong numbers of genes and chromosomes. This is called genetic instability. Having the wrong numbers of genes, or mutated genes, is bad news: it leads to the breakdown of the carefully placed controls and checkpoints in a cell. A cancer cell has specific mutations that allow it to bypass the natural aging process of a cell, and mutations that allow it to acquire immortality.
I said in my last blog that “if cells did what they wanted to, we’d double in size every hour and be spherical.” We’d basically be cancer. But our cells contain an elaborate set of checkpoints that ensure that cell growth does not become unregulated and runaway to form a tumour. At certain points in the cell cycle, a cell is able to biochemically ‘check’ that conditions are well enough for the cycle to continue. If there is something wrong or missing, the checkpoint halts the cell cycle until the damage is repaired. These checkpoints are fascinating – it is incredible to understand exactly how a cell can appear to make a decision. For example, if there is DNA damage a cell decides to stop dividing. How does this happen?
The p53 gene is key to the control of cell growth and is mutated in over 80% of cancers. This is significant: the p53 gene codes for the p53 protein, which is a tumour suppressor protein. When a cell is in trouble, for example if it experiences oxidative stress or DNA damage, multitudes of signalling pathways are activated which culminate in a phosphate group being placed on p53 proteins. This phosphate group causes p53 to change shape. The new p53 shape is able to bind DNA and effect which genes are expressed, for example, causing the expression of the p21 gene and the p21 protein then directly binds and inhibits Cdk2, another protein that causes replication, thus halting the proliferative ability of a cell.
So in a cell where p53 is mutated, if DNA damage or stress occurs, the cell continues to cycle and produce more daughter cells. These cells will also contain the p53 mutation causing them to grow in an unregulated fashion in stressful conditions and so DNA damage, chromosomal abnormality and eventually genetic instability can occur leading to cancer.
It is important to understand that there are thousands of proteins involved in the regulation of cell growth and it is not a mutation in any one of these but a combination of many mutations that leads to cancer. Every person’s cancer is different. Indeed, every cancer cell is different. Cancer is heterogeneous; instead of our beautifully identical and controlled chromosomes, our genome becomes ugly and irregular, with bits added and bits missing.
But cancer cells need to be more than just genetically disorganised. Most cells that procure genetic damage undergo a self destruct programme. Cancer cells are specifically able to evade this programme. They are immortal.
Why haven’t we cured it yet?
Cancer is unbelievably complex and there are many types of cancer for which scientists have only just begun to understand the underlying biology. New high throughput studies involving proteomics (analysis of all the proteins in a cell) or genomics allow us to understand more and more about how cancer cells can be grouped. Grouping genetically similar cancer cells now allows scientists to tailor treatment to that cancer type. But since every cancer is so very different, it is impossible to fully predict how a patient will respond.
Most cancer treatments aim to kill quickly dividing cells. Thus people undergoing chemotherapy lose their hair and have gut and skin problems; the quickly dividing cells in these parts of the body are killed off in addition to the cancer cells. What scientists now need to understand is how to kill cancer cells that grow more slowly but are nevertheless cancerous. These slow-growing cancer cells are often what cause cancer to re-emerge, since a slow-growing cancer cell survives chemotherapy and only need produce one fast-growing daughter cell for a new tumour to develop.
Simply put, cancer research has a long way to go. The science is time-consuming, fiddly and must be firmly backed up by a body of evidence, however, cancer survival is ever increasing and with improved care and dedicated research efforts we will hopefully move towards an age where cancer can be controlled, if not cured.