Scientists at The Institute of Cancer Research (ICR) have for the first time shown that blocking a key enzyme can stop breast cancer spreading to distant organs, according to pre-clinical research published online today in the journal Cancer Research.
The researchers found that the enzyme lysyl oxidase-like 2 (LOXL2) is needed for tumour cells to escape from the breast and invade surrounding tissue, thereby allowing cancer cells to travel to distant organs. They showed that LOXL2 promotes this process by controlling the amounts of molecules called TIMP1 and MMP9, which have previously been shown to play important roles in allowing cancer to spread.
Importantly, using laboratory models, the team showed that blocking the function of LOXL2 decreased the spread of the cancer from the breast to the lungs, liver and bone. These findings confirm that a drug designed to block LOXL2 could be used to treat women with advanced breast cancer.
Lead researcher Dr Janine Erler from the ICR says: “Around 12,000 women die from breast cancer in the UK each year, most because their cancer has spread to other parts of their body. Our study shows that inhibiting the action of LOXL2 can significantly reduce the spread of breast cancer, suggesting that drugs which block this enzyme may be effective in preventing patients’ cancer from spreading.”
The spread of cancer is known as metastasis. Metastatic breast cancer is a complex multi-step process involving the expansion of cancerous cells from the breast to other areas of the body. Once metastases are detected in a patient with breast cancer, median survival is less than two years. It is therefore imperative to develop new therapies to treat patients with highly aggressive breast cancer.
In addition, the team found that LOXL2 could be used to predict whether patients’ breast cancer is likely to be aggressive. Using tissue samples from breast cancer patients, the researchers showed for the first time that high levels of LOXL2 are associated with cancer spread and poor prognosis.
“This raises the possibility that we could develop a test to measure LOXL2 levels and predict patients who will develop aggressive disease. This knowledge could help us tailor treatment type and intensity to individual patients,” says study first author Holly Barker, a postdoctoral fellow in Dr Erler’s laboratory.
Arlene Wilkie, Director of Research and Policy at Breast Cancer Campaign, which funded the study with the ICR and Cancer Research UK, said: “Dr Erler’s results are very exciting, as although currently we can treat breast cancer that has spread, we cannot cure it. By using LOX2 to predict whose cancer will spread and drugs to block the enzyme to stop this from happening, many more lives could be saved. This laboratory research shows great promise and we look forward to seeing how it translates into patients.”
LOXL2 has been linked to the spread of several cancers including colon, esophageal and squamous cell cancers, so the study also has important implications for treating many cancer types.
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “Cancer spread is an important problem in breast and other cancers, and scientists are searching to find new ways to stop cancer spread and save many more lives. The team have shown that targeting the molecule LOXL2, which plays a key role in spread, could offer new approaches to tackle this problem.”
The Institute of Cancer Research (ICR)