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The breast cancer drug-lapatinib, which is designed to shrink tumours can sometimes cause them to grow in the lab, according to a new study. Lapatinib is used in combination with other cancer drugs and chemotherapy to treat patients with an advanced breast cancer, but failed clinical trials as a stand-alone treatment.
Researchers at the Francis Crick Institute, King’s College London and Barts Cancer Institute, Queen Mary University of London, have shown that lapatinib can cause breast cancer cells to grow more rapidly in some situations. 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.
About 20% of breast cancers are caused by a massive excess of a protein called HER2-human epidermal growth factor receptor 2, which sends signals allowing cancer cells to grow and divide. Lots of treatments for HER2 positive breast cancer work by switching off HER2 to make the cells stop growing.
This can be done from outside the cell antibodies such as trastuzumab or inside the cell-kinase inhibitors such as lapatinib. Lapatanib is one of many kinase inhibitors used to treat HER2 positive breast cancers and HER2 is an important target for other existing and emerging breast cancer treatments.
Using a combination of biochemical, biophysical, and computer modelling tools, the team 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.
The HER2-HER3 pair becomes very efficient at allowing the cells to divide than cells that haven’t been treated with the drug. Many breast cancers are triggered by HER2, drugs blocking its action have become important treatments for these diseases and they have shown great success.
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