A drug used in treating non-small cell lung cancer could offer a new targeted therapy for thousands of breast cancer patients, new research has shown.
Scientists at the Institute of Cancer Research in London have established that lung cancer drug crizotinib can kill breast cancer cells that have a particular genetic defect.
They found it can target lobular breast cancers with E-cadherin mutation by using an approach to target tumours known as synthetic lethality.
It is estimated that around 7150 women in the UK are diagnosed with breast tumours that are E-cadherin defective every year.
But despite their prevalence there are currently no treatments that specifically target E-cadherin-defective breast tumours, with little known about what weaknesses exist in these types of cancer cell.
Researchers said that in normal cells, the protein E-cadherin acts like Velcro to help bind them together, but defects in E-cadherin cause cancer cells to grow and divide abnormally.
E-cadherin defects occur in more than 13 per cent of all breast cancer cases, and are seen in up to 90 per cent of all lobular breast cancers, which occur in the areas of the breast that produce milk.
The new research, published in the journal Cancer Discovery, saw scientists test 80 small-molecule inhibitors to see if any of these drugs caused cancer cells with a defective E-cadherin gene to die.
They used synthetic lethality, which exploits two key genes that cancer cells need to survive.
Where one of these two genes does not function properly due to a mutation, blocking the other with a drug has a synthetic lethal effect – causing the cancer cell to die.
They found the most significant synthetic lethality was demonstrated by crizotinib, one of a class of drugs known as ROS1 inhibitors, which killed the E-cadherin defective breast tumour cells and left normal cells relatively unaffected.
A phase two trial is now under way, with researchers hoping it could lead to only the second targeted breast cancer drug to use synthetic lethality, following the PARP inhibitor olaparib.
In 2005, UK scientists from the same lab showed it could be used to target breast tumour cells with defects in two other breast cancer genes, BRCA1 and BRCA2.
Lead author Chris Lord, professor of cancer genomics in the Breast Cancer Now Research Centre at the Institute of Cancer Research, said: “These are hugely promising laboratory findings and we’re very keen to learn whether this class of drug really works as a treatment for women with breast cancer.
“What we have seen so far suggests this is certainly an approach worth pursuing and we are very enthusiastic about the prospect of applying our scientific results in clinical trials.”