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Disappointing breast cancer drug may accelerate cancer cell growth

Thursday May 3rd, 2018

A drug developed to treat breast cancer can accelerate cancer cell growth in some situations, a new study has revealed.

Lapatinib is combined with other cancer drugs and chemotherapy to treat patients with advanced HER2 positive breast cancer, but it has failed clinical trials as a stand-alone treatment.

Researchers say their findings may show why the drug has been disappointing.

A study in eLife carried out by researchers at the Francis Crick Institute, King's College London and Barts Cancer Institute, Queen Mary University of London, UK, have shown that lapatinib can cause breast cancer cells to grow more rapidly in some situations.

Lead author Dr Jeroen Claus, of the Francis Crick Institute, said: "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. Determining these risk factors could help doctors decide which patients may benefit most from these drugs."

About 20% of breast cancers are caused by an excess of HER2 (human epidermal growth factor receptor 2). Lapatanib is one of the kinase inhibitors used to treat HER2 positive breast cancers.

However, the research team found that lapatinib causes HER2 receptors on cell membranes to pair up with HER3. When combined with naturally occurring growth signals from outside of the cell, they can rearrange themselves into an active, signalling pair that tells the cells to divide.

Professor Peter Parker, joint senior author of the paper and group leader at the Francis Crick Institute and King's College London (KCL) said: "Although our study was in breast cancer cells, it gives us new insights into the nuts and bolts of what happens to HER2 when you try to block it and raises some interesting questions around how we should approach designing drugs against HER2 positive breast cancer in the future."

Dr Justine Alford from Cancer Research UK, said this important lab research could guide future work into sophisticated new treatments that target HER2 in a more effective way.

"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," she said.

"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."

Professor Tony Ng, a clinician scientist heading the School of Cancer and Pharmaceutical Sciences at KCL, and joint senior author of the paper, added: "Our new findings could help us design future studies to improve combined HER2 targeted therapies."

Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface eLife 1 May 2018

https://elifesciences.org/articles/32271

Tags: Cancer | Pharmaceuticals | UK News | Women's Health & Gynaecology

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