A drug used to shrink breast cancer tumours has been found to actually increase them in some instances, according to a new study.
In the ongoing fight to find a way to completely eliminate cancers, researchers and pharmaceutical companies are trialling a series of drugs.
Among them is a breast cancer drug called lapatinib, a protein kinase inhibitor used as a targeted treatment for cancers that have large amounts of the protein known as human epidermal growth factor receptor 2 (HER2), which is responsible for cancer cell growth.
The protein accounts for 20pc of breast cancer cases, and lapatinib is used to ‘switch off’ the production of HER2 to stop the cells growing, or cause them to die.
HER proteins combine
However, startling research conducted at the Francis Crick Institute in King’s College London and the Barts Cancer Institute at Queen Mary University of London has shown that the drug can actually cause breast cancer cells to grow more rapidly in some cases.
This could help explain why there has been a number of disappointing outcomes in clinical trials.
In a paper published to eLife, the research team explained that by using a combination of biochemical, biophysical and computer modelling tools, it discovered that lapatinib causes HER2 receptors on cell membranes to pair up with a partner receptor called HER3.
When you combine these inhibitor-induced HER2-HER3 pairs with naturally occurring growth signals from outside of the cell, they can rearrange themselves into an active, signalling pair.
In doing so, the HER2-HER3 pairs become very efficient at telling the cells to divide, even more so than cells that haven’t been treated with the drug.
Improving the outlook for women
“If certain breast cancer drugs can cause cancer cells to grow more rapidly in particular circumstances in the lab, we need to evaluate carefully if that might happen in subsets of patients as well,” said the paper’s lead author, Dr Jeroen Claus. “Determining these risk factors could help doctors decide which patients may benefit most from these drugs.”
Although focused on breast cancer cells, the discovery could help give more insight into the inner workings of what happens to HER2 when you try to block it, and the necessary approach for designing future drugs against HER2-positive breast cancer.
Praising the team’s findings was Dr Justine Alford from Cancer Research UK, who said: “As many breast cancers are triggered by HER2, drugs blocking its action have become cornerstone treatments for these diseases and they’ve shown great success.
“But sometimes, these treatments can stop working, so there is a pressing need to develop new drugs that can overcome this issue and help improve the outlook for these women.”