How does cancer cope with genetic chaos?

As cancers grow, the cancer cells pick up all sorts of changes, errors and mutations in their genes. A huge diversity of cancer cells emerges, making the tumour very hard to treat. Healthy human cells have 23 pairs of chromosomes that package up our DNA. When a cell grows and divides, all the chromosomes are copied And a complete set of 23 pairs is carried across into each of the new cells. But cells can make mistakes For example, accidentally swapping bits of DNA around within or between chromosomes. They might lose parts of chromosomes, or make too many copies Or carry across the wrong number of chromosomes into the new cells This is called Chromosomal Instability, and can contribute to cancer progression and resistance to therapy. Luckily, cells have a number of safety mechanisms in place. Protein molecules check the DNA for faults and stop cells with damaged chromosomes from dividing. If the damage is particularly bad, these safety mechanisms can even force a cell to self-destruct. Researchers at the Francis Crick Institute and UCL, led by Charlie Swanton, have identified new ways in which cancer cells can get around these DNA-checking proteins. One way in which this can happen, they have found, is by blocking a fail-safe that causes cells with faulty DNA to self-destruct. Other new results show that cancer cells with badly damaged genomes have alterations in the machinery that helps chromosomes separate in cell division. The cancer cells take a little longer to divide, which gives them enough time to avoid making excessive mistakes when distributing chromosomes. This avoids activating the cell’s self-destruct button. And in order to keep growing, the tumour selects for the survival of cancer cells that have balanced the amount of healthy chromosomes and faulty chromosomes in their genome. This keeps them in a Goldilocks zone, where the amount of genetic instability is just right. Too little genetic instability, and the tumours can’t evolve and are easier to treat. Too much chromosomal instability and their genomes become too damaged and they can’t divide any more. So the tumour environment selects cancer cells that stay in the Goldilocks zone where the amount of genetic instability is just right for them to keep evolving and escape treatments that suppress cancer growth. But if we can tip the balance to either extreme we could push cancer cells out of their Goldilocks zone. By either allowing the faulty parts of the genome to mend or increasing the faults so the cancer cells are too damaged to keep growing we might have a better chance of stopping cancer growth and drug resistance.

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