An experimental drug can shrink tumours caused by a genetic mutation responsible for many cancers, opening the door to greater personalised treatment of the disease.
Up to one in four human cancers have a mutation in the KRAS gene, which is responsible for a protein that controls cell growth. These mutations can cause normal cells to grow out of control, leading to cancer.
“Patients with KRAS mutant tumours generally have a poorer prognosis and have lacked effective treatments,” says Jude Canon of the biopharmaceutical company Amgen.
Yet finding a way to target this protein has remained elusive since its discovery over 30 years ago.
Canon and his colleagues made a breakthrough when they found a groove on the surface of the KRAS protein with one of the common mutations – the G12C mutation. This allowed them to develop a drug that selectively binds to the mutant protein and stops it working.
The G12C mutation is found in around 13 per cent of lung adenocarcinomas, a type of non-small-cell lung cancer, 3 per cent of colorectal cancers and 2 per cent of other solid tumours.
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When the researchers tested the drug, called AMG 510, they found that eight out of 10 mice became cancer free with a high dose.
The team also studied the effects of the drug on four people with non-small-cell lung carcinoma. After six weeks, one person on a 180 milligram dose had their tumour shrink by 34 per cent, and another taking a 360 milligram dose saw their tumour shrink by 67 per cent.
The cancer didn’t increase or decrease in the other two people, who both took 180 milligram doses.
Canon and his colleagues also found that AMG 510 appears to prime the immune system against the cancer. After the drug had removed tumours from mice, the team tried to inject new tumour cells. But their bodies wouldn’t grow the tumour cells, suggesting the immune system had adapted.
“This is a remarkable observation,” says Simon Conn at Flinders University, Australia.
By pairing with genetic profiling, this drug provides the best candidate so far for improving personalised treatment of a range of common and rare cancers, particularly non-small-cell lung carcinoma, says Conn.
Journal reference: Nature, DOI: 10.1038/s41586-019-1694-1
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