Scientists unlock key to tamoxifen resistance

Cancer Research UK

Cancer Research UK funded scientists have discovered why some breast cancers are resistant to the commonly used drug tamoxifen, their findings are published in Cancer Research.

Tamoxifen is given to most women for around five years after they are diagnosed with breast cancer to help prevent the disease from coming back. Some women gradually develop resistance to the treatment meaning their cancer is more likely to return. This discovery could lead to new drugs that counteract this resistance.

The team of scientists in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) found that when a gene called FGFR1 is turned on too much it causes resistance to tamoxifen and other hormone treatments.

When stimulated in this way breast cancer cells no longer rely on hormones to grow rapidly and spread, making hormone treatments like tamoxifen less effective.

Around a tenth of breast cancers have too much of the FGFR1 gene and these patients are more likely to see their cancer return after initial treatment and have a poor prognosis. But until now it wasn’t known whether FGFR1 was behind this poor prognosis. Understanding the role that FGFR1 plays could help personalise treatments for women.

In lab studies the scientists were able to switch off FGFR1 in cancer cells with too much of the gene, by adding a drug that blocks the function of FGFR1. Once FGFR1 was switched off hormone treatments were once more able to work and destroy the cancer cells. Understanding more about switching off FGFR1 could lead to new treatments that benefit patients who do not respond to tamoxifen.

Lead author Dr Nick Turner, a Cancer Research UK funded clinician scientist from the ICR, said: “We have known for some time that breast cancer patients with too much of the FGFR1 gene in their cancer are more likely to have a poor prognosis, but we did not know if FGFR1 was behind this. Understanding how this gene can cause tamoxifen resistance reveals a new drug target for treating breast cancers in patients who would otherwise have a poor outcome.

“There are a number of drugs in development that stop FGFR1 working, and clinical studies are investigating whether these drugs work against cancers with too many copies of this gene."

“The next step is to set up a clinical trial to see whether a drug that blocks the action of this gene can counteract hormone therapy resistance in breast cancer patients. If these trials confirm our lab work we could be on the verge of a potentially exciting new treatment for breast cancer.”

Breast cancer is the most common cancer in the UK affecting more than 45,500 women each year.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, said: "This new work provides another good example of how in the Breakthrough Centre we combine biological research with clinical application for patient benefit."

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This research shows the importance of understanding how a patient’s response to treatment is defined by the genetic makeup of a tumour and how this changes over time. And it points the way to new treatment strategies targeted to this group of patients. Cracking the problem of resistance to treatments such as tamoxifen would be a major advance in treating breast cancer.”

ENDS

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References

  • Turner, N., Pearson, A., Sharpe, R., Lambros, M., Geyer, F., Lopez-Garcia, M., Natrajan, R., Marchio, C., Iorns, E., Mackay, A., Gillett, C., Grigoriadis, A., Tutt, A., Reis-Filho, J., & Ashworth, A. (2010). FGFR1 Amplification Drives Endocrine Therapy Resistance and Is a Therapeutic Target in Breast Cancer Cancer Research, 70 (5), 2085-2094 DOI: 10.1158/0008-5472.CAN-09-3746