Augmenting investigational drug xentuzumab could boost oestrogen receptor-positive breast cancer cell death, according to new findings


UK researchers have discovered a way to potentially augment the effectiveness of the investigational drug, xentuzumab, for the treatment of oestrogen receptor-positive (ER+) secondary breast cancer.

Previously, the team had found that blocking insulin-like growth factor (IGF) could delay the proliferation of breast cancer cells by slowing DNA replication. To further investigate this effect, researchers conducted a compound screen using luminal ER+ breast cancer cell lines to identify additive or synergistic drug combinations with xentuzumab, an IGF-neutralising antibody.

The findings, published in the journal Oncogene, show that treating breast cancer cells with xentuzumab and an inhibitor of the protein CHK1 (MK-8776 and SRA737) or WEE1 (MK-1775) almost completely arrests DNA replication. This results in substantial accumulation of unreplicated single-stranded DNA, prompting cancer cell death at a much higher rate. The authors believe this approach could pave the way for new effective therapies involving IGF blockers in combination CHK1 or WEE1 inhibitors.

‘Promising option’ for ER+ breast cancer

Commenting on the findings, lead author Dr Valentine Macaulay, University of Oxford, said: ‘Our new discovery proves that we can exploit this finding to kill breast cancer cells more effectively. We hope these new findings will help to develop new combination treatments for people with breast cancer, by targeting processes that are essential for cancer cell growth.’

Nearly 35,000 patients are likely to be living with secondary breast cancer in the UK, the majority of them being ER+ cases. Dr Simon Vincent, Director of Research, Support, and Influencing at Breast Cancer Now, said: ‘We hope these discoveries lead to urgently needed new and effective treatments that will stop people with incurable ER+ secondary breast cancer dying from this devastating disease.’

The research was funded by Breast Cancer Now and Cancer Research UK. Valentine Macaulay is a Consultancy Board Member for Boehringer Ingelheim. One author is an employee and another an ex-employee of Boehringer Ingelheim. The remaining authors report no competing interests.

This article originally appeared on Medscape, part of the Medscape Professional Network.


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