Cheap drugs to treat parasitic worms and conditions such as river blindness could be used for women with a type of breast cancer that often fails to respond to standard therapies, a new study shows.
Scientists at The Institute of Cancer Research, London, found that a class of drugs used to treat parasite-borne illnesses block the interactions of a protein important in triple-negative breast cancer.
They found that in breast cancer cells, the drugs prevented the protein SIN3 from binding to other proteins, and that this blocked tumour growth and stopped the cancer spreading.
The drugs, which are cheap and available worldwide, also made the cells sensitive to a common hormone therapy, opening up the possibility that they could be used in combination to treat triple-negative breast cancer.
The study, published in the journal Molecular Cancer Therapeutics, was funded by Leukaemia and Lymphoma Research, with additional funding from Worldwide Cancer Research.
Triple-negative breast cancer accounts for 10–20% of all breast cancer cases, but it can be more difficult to treat than other forms of the disease because it doesn’t respond to hormone therapy or targeted treatments like Herceptin.
The disease is thought to be caused in part by epigenetic changes – where genes are not mutated but are switched on and off in cells – and a key driver of these is SIN3.
Scientists analysed the molecular structures of 2,000 clinically approved drugs to identify chemical targets that could interact with SIN3 and stop it binding with partner proteins.
They found that two drugs, which are part of a family of compounds called avermectins and act as anti-parasite medication, were able to block SIN3 activity.
In breast cancer cells, the two drugs silenced genes associated with the growth of tumours and their spread to other parts of the body.
In mice with triple-negative breast cancer, treatment with one of the drugs shrunk tumours, and reduced the likelihood that they would spread to other areas like the lungs.
The findings suggest that the drugs could be a cheap and effective way to treat triple-negative breast cancer, and could be combined with other breast cancer treatments for improved outcomes.
Dr Chris Lord, Leader of the Gene Function Team at the ICR, said: “Triple-negative breast cancers are often difficult to treat as some of the existing treatments fail to work in this form of the disease. So it’s exciting to discover that two cheap, readily available drugs could be effective treatments.
“We found that drugs called avermectins, which are used to treat parasitic diseases like river blindness, were able to bind to a protein implicated in the progression of triple-negative breast cancer. They silenced genes important for breast tumours to grow and spread, while activating genes that sensitise cancer cells to the common hormone therapy tamoxifen.
“Our results suggest that these drugs could offer an exciting, cost-effective way to treat triple-negative breast cancer, either on their own or in combination with other treatments already in use. It would be very interesting to see whether these drugs work as well in patients as they do in mice.”