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Leading Glasgow scientists will investigate if an existing drug devimistat, which is currently being tested for treating other types of cancer, could also be used to treat thousands of women with breast cancer.
Researchers funded by Breast Cancer Now will trial using the drug as part of a completely new approach to treating triple negative breast cancer, a type of breast cancer which tends to be more aggressive and disproportionately affects younger women and black women.
Breast tumours are made up of more than just cancer cells, and cancer cells can trick nearby healthy cells into helping tumours grow. Such example is cancer-associated fibroblasts (CAFs). This type of non-cancer cell is found in large numbers inside breast tumours and can make molecules that influence the behaviour of cancer cells. CAFs have been shown to help breast cancer cells not only grow, but also move to other parts of the body where the disease becomes incurable.
The new study, funded by Breast Cancer Now, will be led by Professor Sara Zanivan from the Beatson Institute for Cancer Research. Professor Zanivan previously discovered that CAFs found in triple negative breast cancer can support cancer cell growth by making high amounts of a protein called PDH. Now, Professor Zanivan and her team will study how high amounts of this protein can help breast cancer cells spread. The researchers will also test (in mice) if devimistat can be used to target this protein and treat triple negative breast cancer.
Around 4,700 women are diagnosed with breast cancer in Scotland every year, and 15% of these cases (over 700 Scottish women) will be triple negative. Triple negative breast cancer refers to a diverse group of breast cancers that lack the three molecules which are normally used to classify the disease: the oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
While these molecules have been used successfully to develop a variety of targeted treatments for other types of breast cancer, the absence of these molecules in triple negative breast cancer means that its treatment is mostly limited to a combination of surgery, chemotherapy, and radiotherapy, which can come with gruelling side effects.
Existing breast cancer treatments either directly target cancer cells or affect all rapidly growing cells in the body, often causing harsh side effects. Targeting other cells that are known to support the spread and growth of cancer offers a new and exciting approach to treating the disease. Rather than trying to destroy cancer-assisting cells, Professor Zanivan and her team are investigating a way to stop these cells supporting cancer growth.
Professor Sara Zanivan, study lead at the Beatson Institute for Cancer Research, said:
“We know that breast cancer cells communicate with other non-cancer cells nearby, which helps breast cancer tumours grow and survive. It’s really important that we continue to increase our understanding of this activity, as it may uncover much needed new ways to treat the disease.
“My team will genetically change cancer-associated fibroblast (CAF) cells donated by people with triple negative breast cancer to reduce the levels of the PDH protein in them and investigate if this prevents cancer from growing and surviving. We will then test whether the drug devimistat can make the PDH protein less active and see if this has the same outcome. We envisage that targeting non-cancer cells alone, or in combination with current therapies, could halt the growth of triple negative breast cancer."
Dr Kotryna Temcinaite, Senior Research Communications Manager at Breast Cancer Now, said:
“Over 700 Scottish women are diagnosed with triple negative breast cancer each year. There are limited targeted treatments available to treat this type of breast cancer, which is why we desperately need new and effective treatments, so we can stop people dying from this devastating disease.
“The knowledge we’re gaining from Professor Zanivan’s research gives us real hope for the future. With a greater understanding of how triple negative breast cancer cells grow and survive, we can find new ways to stop breast cancer tumours spreading and becoming incurable.
“Our world-class research is only possible thanks to public support. Due to the impact of the COVID-19 pandemic our fundraising income fell, meaning we are less able to fund new research that could transform the lives of people affected by breast cancer. We need your support now more than ever – please donate at: www.breastcancernow.org/donate.”
Janette Campbell, from Glasgow, was diagnosed with triple negative breast cancer in 2009 at 44-years-old. In 2012 she was told the disease had spread to her chest wall and in 2014 tests showed the cancer had spread to her lungs.
“In 2009 I was told I have triple negative breast cancer. The diagnosis was pretty scary, my oncologist said the cancer would come back within a year and I wouldn’t survive five more years. I was told my only hope was chemotherapy and there were no other options after that. The way I was told about triple negative breast cancer felt like a death sentence.
“In 2012 a PET scan picked up cancer in my chest wall, then in 2014 routine tests showed the cancer had moved to my lungs. I didn’t know that the cancer moving to another part of the body made it terminal, but after the cancer came back I was told it is and that I would need to be on chemo for the rest of my life.
“Triple negative breast cancer is a very scary cancer. The survival rate is so low, I was diagnosed 12 years ago but sometimes feel like I shouldn’t be here. Generally, I feel positive day to day, but I have been through a lot of hospital appointments with different girls with triple negative who are no longer here.
“This research from Breast Cancer Now would have given me a lot of hope when I was first diagnosed. Triple negative breast cancer is so aggressive that I was prepared for the cancer to come back, but the more research done into this disease the better. Rather than just relying on chemotherapy we need more options for women who are diagnosed, and hopefully this research can find new ways to treat the disease.”