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Biomarker for therapy resistance in HER2 positive breast cancer
A new study from researchers in Trinity College Dublin could help predict and overcome resistance to the HER2 targeted cancer drug Herceptin and other newer anti-HER2 drugs. The results of the study, published in the journal Cancer Research, indicates that an extracellular vesicle biomarker called neuromedin U (NmU) is strongly associated with resistance to hercepin and newer drugs against HER2 positive cancers.

Levels of HER2, one of the family of receptors for epidermal growth factor, are elevated in about 25% of breast cancer patients. HER2 positive breast cancer is associated with relatively poor prognosis. However, a number of HER2 cancer targeted drugs have become available in recent years, among them the well-known Herceptin, but also including newer examples such as lapatinib, neratinib, afatinib, pertuzumab and T-DM1.

While these drugs are effective in many HER2 positive breast cancer patients, others are resistant to these therapies or develop resistance over time. Dr Lorraine O’Driscoll, senior author on the study, explains the problem further: "Many patients with HER2 positive tumours gain huge benefit from these drugs. Unfortunately, however, some who seem suitable candidates based on a HER2 test, don't gain the maximum intended benefit from these treatments. They may have a natural level of resistance to the treatment which is not detectable with currently available tests, while some other patients respond at first but may then become unresponsive or develop resistance to the treatments."

Thus there is an urgent need for biomarkers which could predict which patients are likely to be responsive to Herceptin and other anti-HER2 positive cancer drugs. This is where the new finding of a strong association between NmU and resistance to these drugs may be of vital importance. Furthermore, the blood levels of NmU are reflective of the intracellular levels, introducing the possibility of a minimally invasive blood test to measure NmU levels when considering the treatment options in patients with HER2 positive breast cancer.
In functional tests, the research team discovered that adjusting the levels of NmU could restore sensitivity to Heceptin and other anti-HER2 drugs. Also, blocking NmU could significantly reduce tumour growth. Studies are ongoing in this area. Meanwhile, the group has two patents pending in the USA and in Europe, in the context of facilitation of translation of their discoveries for patient benefit. This will be helped by the team's collaboration with the All Ireland Oncology Research Group (ICORG).


Rani, S., Corcoran, C., Shiels, L., Germano, S., Breslin, S., Madden, S., McDermott, M. S., Browne, B. C., O'Donovan, N., Crown, J., Gogarty, M., Byrne, A. T., and O'Driscoll, L. (2014). Neuromedin u: a candidate biomarker and therapeutic target to predict and overcome resistance to HER kinase inhibitors. Cancer Research. Cancer Research (29 May 2014), doi:10.1158/0008-5472.can-13-2053

Press release: Trinity College Dublin, available from
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