What is cancer? Everyone knows that it is a terrifying disease and has some ideas about a mass of cells that grow uncontrollably but I get the feeling that many people don’t quite understand how it actually happens. I think that even from my biochemistry and cell biology lectures I’d still have a very woolly appreciation of what’s important when it comes to cancer. Before I start with the science, I have to recommend “The Hallmarks of Cancer” by Hanahan and Weinberg – it’s a very readable review that neatly organises cancer biology and was written to help usher in a new way of thinking about cancer.
Cancer can be thought of as being evolution in action. Very simply put: if something replicates faster than its siblings it will dominate its environment, a fact that is as true of cells as it is of rabbits. However, in the human body, with its exquisite regulation of functional tissues and organs, replication is normally kept under control and almost all cells divide very slowly or not at all. Why is this? Because the somatic (i.e. body) cells do not contribute to the next generation, only the germ line cells (which make sperm and eggs) do. Thus there is no evolutionary competition between cells (c.f. ant colonies: the workers are sterile and do not contribute to the next generation, so there’s no evolutionary competition between them and they’ll willingly sacrifice themselves for the colony) – they don’t try to outgrow each other and dominate their organ, because that would be bad for the organism and their genetic material would not be passed on to the next generation. The problem is that evolution is blind so there’s no ‘trying to outgrow’ or foresight involved. If one cell looses the shackles that stop it from replicating it will replicate, causing cancer. It doesn’t ‘know’ that it will only be able to replicate until the organism dies, at which point all its progeny will die too. The effects of natural selection don’t stop there though: one mutation may allow a cell to ignore one signal to stop dividing, but if one of the group of dividing cells acquires another mutation that allows it to divide even faster, then its progeny will come to dominate the tumour.
So what are the changes that cause cancer, and why do they occur? As I’ve just alluded to, we’re talking about mutations – changes to the signal transduction pathways that tell the cells what to do. Mutations happen for all sorts of reasons, most commonly because DNA replication (required for every cell to divide) makes mistakes. Certain things, such as UV light (in sunshine) and many of the components of cigarette smoke also cause mutations and so can increase the likelihood of cancer developing. However, many of the other substances that have been touted as ‘causing cancer’ (c.f. the Daily Mail) have only very mild effects if any.
Simply replicating faster isn’t enough for a cell to become cancerous. Its progeny will still mature and eventually stop growing as they differentiate into skin cells or white blood cells or whatever. In addition, when the body notices the cancer, the immune system will tell the cells to “commit suicide” – i.e. undergo apoptosis. If it forms a lump of cells, there won’t be a blood supply so the ones in the centre will die. After a certain number of divisions, cells slow down and enter ‘senescence’. What I’m trying to say is that one mutation in a single pathway is not enough to create a tumour and kill you. There are several ‘hallmarks’, or characteristics that a potential cancer cell needs to acquire through different mutations in different pathways. These are:
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis (so the cells cannot “commit suicide”)
- Limitless replicative potential (immortality – most cells can only divide a finite number of times)
- Sustained angiogenesis (creating a blood supply to the tumour)
- Tissue invasion and metastasis (this is what kills people, when the tumour invades surrounding areas, bits fall into the blood stream and grow in other parts of the body)
Only once some of the cells of a tumour acquire all these characteristics do you have a full-blown aggressive cancer.
In the following posts on this topic I’ll talk about cancer therapies, leukemia and other types of cancer, as well as the mechanisms of some of the more “popular” cancers (colon, breast, cervical and prostate) and what is meant by predisposition to certain cancers.