Scientists discover genes driving resistance to breast cancer drugs

UK scientists have discovered a number of genes which are responsible for developing resistance to a targeted medicine used in the treatment of HER2-Positive breast cancer. 

The team at the Institute of Cancer Research in London examined a number of genes that were overactive in women with HER2 Positive breast cancer who had developed a resistance to the drug Lapatinib (Tykerb).

Around 20 per cent of breast cancers are HER2 Positive and the targeted medicines Herceptin and Tykerb are most commonly used to treat women with this type of cancer.  However, in some women a drug may stop being effective after being used for a certain period of time.

This latest research, funded by Breakthrough Breast Cancer, found several genes which change the way the Tykerb works.

Study co-author Dr Chris Lord a senior staff scientist at the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research, says the discovery will help to develop and improve the way doctors treat breast cancer.

“We have identified several genes which appear to play a role in resistance to certain drugs. We can use this knowledge to help us develop new targeted therapies for breast cancer patients. Further investigation will be needed before reaching clinical trials but we are confident in the exciting results displayed so far.”

The scientists studied 369 genes which show high level activity in HER2-Postive breast cancers. They disabled these genes individually to see what effect each inactivated gene had on the effectiveness of the Tykerb. Using this method, the scientists have identified several genes such as NIBP, PTEN and RAC1 which, when inactivated, change the way breast tumour cells respond to drugs.

The head of research at Breakthrough Breast Cancer, Richard Francis, says it can be very daunting for women when drugs cease to work.

"This discovery is crucial as in the future it will help us to ensure that drugs, such as Tykerb and Herceptin, continue to treat patients successfully. We are dedicated to discovering new and better therapies for the disease to ensure patients receive effective treatments and care.”

BCAC chair, Libby Burgess, says understanding the genetic mechanisms of drug resistance is an exciting area of research that will lead to the development of more effective breast cancer treatments.

“This is the way of the future.  Researchers are unlocking the potential to identify and target the specific genes involved in the growth and spread of each sub-type of breast cancer, both when it is first diagnosed and then down the track if and when the cancer becomes resistant to the drugs used. This will enable researchers to find ways of shutting down the processes that drive the growth and spread of different types of tumours," Libby says.

"It will allow for the development of therapies that can be tailored to overcome drug resistance and effectively treat an individual’s particular type of breast cancer over many years. That’s an incredibly promising and powerful approach that will ultimately transform cancer from a deadly disease into a highly treatable one."

BCAC looks forward to clinical trials that further explore this exciting new approach. 

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