12 March 2013
Scientists have discovered a potential new way to overcome the resistance many women develop towards a treatment for a common type of breast cancer.
The research, funded by Breakthrough Breast Cancer and conducted at the Institute of Cancer Research, London, highlights several genes that appear to play a key role in allowing cancer cells to become resistant to treatment. The results, published in the journal Oncogene, open up potential new strategies to bolster the effectiveness of cancer drugs.
HER2 positive cancers account for 15-20% of all breast cancers in the UK, affecting around 10,000 patients each year. HER2 is a protein which, when present at high levels, can play a major role in causing breast cancer cells to grow and multiply.
While there are some effective treatments for HER2 positive breast cancer some patients can build up resistance to commonly used drugs such as Herceptin and Lapatinib. This study looks specifically at the drug Lapatinib, with scientists discovering several genes which change the way the drug works.
Study co-author Dr. Chris Lord, Senior Staff Scientist, Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, says: “This research will help us to develop and improve the way we 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 breast cancers. They disabled these genes individually to see what effect each inactivated gene had on the effectiveness of the drug Lapatinib. 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.
Fellow study author Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: “Our work shows how cutting-edge genetic techniques can help us pinpoint the molecular sources of drug resistance in cancer cells. It opens the way to new ways of combatting drug resistance by supplementing existing breast cancer treatments. And now we know this approach works, we can use it to understand drug resistance in other types of tumour too.”
Richard Francis, Head of Research at Breakthrough Breast Cancer, says: “Unfortunately some breast cancer drugs stop working over time in certain patients, which can be a daunting experience for these women.
"This discovery is crucial as in the future it will help us ensure that drugs, such as Lapatinib 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.”
This research was funded by Breakthrough Breast Cancer and AACR/Stand Up To Cancer.
D Wetterskog, K-K Shiu, I Chong, T Meijer, A Mackay, M Lambros, D Cunningham, J S Reis-Filho, C J Lord and A Ashworth. Identification of novel determinants of resistance to lapatinib in ERBB2-amplified cancers. Oncogene advance online publication 11 March 2013.