Protein may provide target for new breast cancer therapies

In collaboration with Adfero

An international research team, led by scientists at Imperial College London, have identified a protein that appears to be involved in the development of drug resistance in breast cancer.

The protein, called LMTK3, could one day provide a target for the development of new therapies if this early laboratory research is confirmed by further studies.

Hormone-blocking drugs such as tamoxifen are commonly used to treat women whose breast tumours require oestrogen to grow, but their cancers become resistant to the therapy over time.

The researchers, whose findings are published in the journal Nature Medicine, found that LMTK3 helps to 'switch on' the response to oestrogen in tamoxifen-resistant breast cancer cells, counteracting the effectiveness of the treatment.

Blocking LMTK3 'switches off' the response, making cancer cells more sensitive to the effects of hormone-blocking drugs.

Next, the team measured the levels of LMTK3 in samples of breast cancer tissue taken from women with the disease.

They found that women with higher levels of the protein in their breast cancer cells tended to have a shorter life expectancy and were less likely to benefit from hormone therapy.

Certain faults in the gene for LMTK3 were found to be linked to how long an individual survived.

Finally, the researchers also studied mice carrying breast tumours that were resistant to tamoxifen. Using an experimental genetic technique to switch off LMTK3, they were able to shrink the size of the tumours.

Senior author Professor Justin Stebbing, from Imperial College London's Department of Surgery and Cancer, said: "Anti-oestrogen drugs have been very successful at allowing women with breast cancer to live longer, but resistance to these drugs is a common problem.

"Our results suggest that the action of LMTK3 on the oestrogen receptor has a crucial role in the development of drug resistance.

"We're now looking for drugs that can block the effect of LMTK3, which we could hopefully give to patients to prevent them from becoming resistant to hormone therapy. It will probably take at least five to ten years to develop new treatments that are safe to be used in humans."

Dr Kat Arney, science information manager at Cancer Research UK, said: "These new results reveal a 'switch' that helps to explain why some breast cancers become resistant to hormone drugs, and could lead to new ways to combat this in the future.

"But it's important to point out that these experiments have been done using animals, cells and tumour samples in the lab, so there's still a long way to go before we're even close to a drug that could be used to treat cancer patients."

References

Giamas G et al. Kinome Screening for Regulators of the Estrogen Receptor Identifies LMTK3 as a New Therapeutic Target in Breast Cancer. Nature Medicine (2011)