Lung cancer often isn’t spotted until it has started to spread through the body. This can make the disease difficult to treat, leading to a very poor survival rate. Now scientists in the US have found that damage to a gene called LKB1 might be the key event that fuels the spread of lung cancer.
There are many genes implicated in cancer, and a big challenge for scientists to figure out which gene does what. LKB1 is one of these ‘cancer genes’. In healthy cells it protects us from the disease – it’s a type of gene known as a tumour suppressor.
But faults in LKB1 can lead to cancer. For example, we know that people who inherit faulty copies of LKB1 are more likely to develop several types of cancer – a condition called Peutz-Jeghers syndrome. And faulty LKB1 has also been spotted in some non-inherited cases of lung cancer.
But decades of cancer research have taught us that, for cancer to develop, cells must pick up several faults in different genes.
So to test how LKB1 fits into this picture, scientists did some cross-breeding experiments with mice. They started with a breed of mice carrying an overactive version of a gene called Kras (also known as Ras) that can increase the likelihood of certain cancers. This faulty gene effectively “short circuit” the controls on cell multiplication, so cells start to multiply out of control. The researchers then bred these faulty Kras mice with another strain carrying faults in the LKB1 gene.
More specifically, these mice had been genetically engineered so that faults in LKB1 and Kras can be specifically produced only in lung cells. This is achieved by some pretty clever technology. The upshot is that a small number of cells in the mice’s lungs end up with faults in both genes, so scientists can see the combined effect of both at once.
They found that the double-fault mice developed highly aggressive lung tumours that quickly spread, compared with mice carrying only faulty Kras. To use a metaphor, the LKB1 fault acted like throwing petrol on a fire (Kras), causing it to burn rapidly out of control.
And when the team looked in human and mouse lung cancer cells, they found that shutting off LKB1 switched on loads of genes that make cancer cells spread.
So by studying the interaction of these gene faults, the researchers have shed some light on what makes some lung cancers grow so aggressively. And the new mice they have produced might be a good model for studying lung cancer in the lab, accelerating the pace of research towards much-needed treatments.
But could we ever use LKB1 for treating cancer? Maybe – if scientists can find a way of reactivating or mimicking its function in cancer cells.
Perhaps more interesting is the possibility that LKB1 could be used as a prognostic tool – helping doctors to predict how an individual patient might respond to treatment, or how their cancer will spread. But work like this needs to go hand in hand with better ways to pick up lung cancer at an earlier stage – something that is a big problem at the moment. It isn’t very helpful to be able to tell someone that they have an aggressive cancer if it has been detected too late for effective treatment.