A leading Sheffield scientist has been awarded a grant worth almost £200,000 by Breast Cancer Now to fund cutting-edge research that aims to stop breast cancer spreading to the bone.
If breast cancer spreads around the body – known as secondary breast cancer – it becomes incurable. Over 1,000 women in South Yorkshire are diagnosed with breast cancer every year, and more than 220 women in the region die from the disease each year.1 The majority of the 11,500 women who die as a result of breast cancer each year in the UK will have seen their cancers spread.
The bone is one of the most common places for breast cancer to spread to, with around 70% of secondary breast cancer patients having tumours in the bone. Cancer in the bone can cause joint pain as well as debilitating fractures that often require surgery at a time that is already difficult for patients.
With previous Breast Cancer Now funding, Professor Alison Gartland, based at the University of Sheffield, helped make the significant discovery (published in Nature in May 2015) that a molecule called lysyl oxidase (LOX), which is released by primary breast tumours, is responsible for making holes in bones. These holes help prepare or ‘prime’ bone for the arrival of breast cancer cells, increasing the tendency of cancer cells to spread there.
Professor Gartland’s team, from the University’s Department of Oncology and Metabolism, will now investigate how a second molecule – P2X7R – interacts with LOX to help breast cancer spread, and whether it could be targeted with drugs to stop breast cancer spreading.
Alison Gartland, Professor of Bone and Cancer Biology, said:
“With previous funding from Breast Cancer Now, we made the exciting discovery that LOX plays a critical role in helping secondary breast tumours form in the bone. We have since found that P2X7R can work with LOX to prepare the bone environment for the arrival of secondary cancer cells, so this Breast Cancer Now grant will enable us to investigate this further.
"We hope to find out whether drugs that block P2X7R, which have already been shown to be safe in clinical trials for arthritis, could prevent cancer spreading to the bone. This would be of great benefit in the fight against this horrendous disease that has such devastating effects."
Firstly, the team will study how P2X7R interacts with LOX in individual bone cells, before examining how drugs that block P2X7R modify the effect of LOX on bone tissue. By doing this the team hopes to establish whether LOX is only able to prime the bones in the presence of P2X7R, and will investigate whether any other molecules are also involved in helping cancer to spread.
Next, the research team will test the effects of drugs that block P2X7R and LOX using mouse models of primary and secondary breast cancer. They will use micro-CT scans to assess the number and size of the holes in bone following this treatment, as well as taking blood samples to measure levels of LOX and other molecules that indicate possible spread to the bone. They will also analyse tumour growth across a variety of metastatic sites, to assess the effects of blocking P2X7R on the formation of secondary tumours.
Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now, said:
“If we are to stop people dying from breast cancer, we must find a way to prevent the disease spreading. Professor Gartland’s research could help uncover which molecules are vital in helping breast cancer spread to the bones, and identify drugs that might stop this happening.
“Drugs that target P2X7R are already being trialled for treating arthritis, and so this could be a promising avenue of research into preventing the complex process by which breast cancer spreads and becomes incurable.”
1 Source of information: Incidence, mortality, and survival statistics were obtained from the Health and Social Care Information Centre. Incidence statistics were based upon women diagnosed between 2011 and 2013. Mortality statistics were based upon women dying from breast cancer between 2012 and 2014.