When copying 6.3 billions base pairs mistakes are bound to happen
When cells divide all the DNA is copied, letter-by-letter, for the new cell. That in itself doesn’t sound like much – to comprehend how huge this undertaking is you have to understand just how long the human genome actually is. Scientists at the University of Leicester have printed out the whole human genome – it is 130 volumes long and would take 95 years to read! To copy this vast amount of information takes the fastest dividing cells just 8 hours. And with all that copying, and working that fast, mistakes are bound to happen.
Mistakes in the DNA are called mutations and can lead to cancer. Fortunately, cells have a few fail-safes that help stop this. Cells can correct damage in their DNA – they read it and replace mistakes just like you would edit a typo. Cells will also put a halt on cell division until all the mistakes have been corrected.
But sometimes the DNA is just too damaged to correct and, like in any good sci-fi film, if all else fails there is a self-destruct sequence. Cells that are beyond repair will destroy themselves to prevent mutations turning them cancerous. This happens all the time in normal tissue and is called apoptosis – a damaged cell will self-destruct and a neighbouring cell will divide producing a new healthy cell to fill the gap.
How do cells become cancerous?
With this fail safe in place, how does a cell become cancerous? One of the ‘Hallmarks of Cancer’ is its ability to evade apoptosis. Many cancers produce too many ‘survival proteins’ – such as BCL-2 that promotes cell survival by blocking cell death. Expression of BCL-2 in cancer makes cells more resistant to therapy – such as chemotherapy and radiotherapy – and makes this protein a target for new drug discovery.
Cancer cells also avoid apoptosis by having mutations in proteins that cause the cell to self-destruct. p53 is one of these proteins and is interesting because it plays a dual role in this story. This protein controls the breaks – slowing the cell down and giving it time to correct mistakes in the DNA – and, when repair is not possible, p53 will induce apoptosis. A mutation in the p53 protein will mean that the cell does not slow down to correct mistakes, which will start to accumulate, and when the cell becomes badly damaged it will have no self-destruct button.
Recent research has highlighted the importance of the p53 protein in breast cancer. Up to 70% of breast cancers are ‘oestrogen receptor positive’ – that is they have this receptor at the surface and are dependent on oestrogen hormone for growth. New research has found that this receptor can deactivate p53, allowing the cell to evade apoptosis. Knowing this may lead to an another way to target and kill these breast cancer cells, and continue to improve survial for patients with this disease.
Scientist have also been working on the way we target ‘survival proteins’ that are over-expressed in cancer. The idea is that, by switching off proteins like BCL-2, the cancer cells will be unable to evade apoptosis and will die. However, drugs that target these survival proteins have some pretty nasty side-effects. Recently, researchers in America have been re-designing the drugs that switch off BCL-2. A new compound, ABT-199, has been made that more specific targets BCL-2 – the hope is that this drug will have less severe side effects.
As our understanding cancer cells increases, scientists are finding more and more chinks in their amour. And, with all these new targets to aim for, it’s only time before we cure cancer.
Bailey, Shannon T., et al. “Estrogen receptor prevents p53-dependent apoptosis in breast cancer.” Science Signaling 109.44 (2012): 18060.Souers, Andrew J., et al. “ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.” Nature medicine (2013).
Souers, Andrew J., et al. “ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.” Nature medicine (2013).