Drug accelerates cell division in aggressive breast cancers
UK researchers are developing a new type of drug that blocks one of cancer’s key evolutionary escape routes from chemotherapy and could be used to treat aggressive breast cancers, reinvigorating the response to chemotherapy in cancers that have become resistant.
Known as BOS172722, the drug was discovered at The Institute of Cancer Research (ICR) in the Cancer Research UK Cancer Therapeutics Unit. It works by blocking a molecule called MPS1, which plays a central role in controlling cell division — the drug thus forces cancer cells through cell division too quickly, leading to fatal errors in parcelling out DNA.
MPS1 is involved in organisation of chromosomes during cell division, ensuring they are distributed correctly between daughter cells and making sure that cell division doesn’t go ahead until they have been parcelled out evenly. By blocking MPS1 using the new drugs, cancer cells speed through cell division with the wrong number of chromosomes and die as a consequence.
The ICR researchers found that cancer cells in dishes treated with the MPS1 inhibitor went through cell division in just 11 minutes, compared with 52 minutes without the drug. Fast-dividing cells, from triple negative breast cancers as well as ovarian and lung cancers, were especially sensitive to the effects of blocking MPS1.
Phase I trial underway
The drug is being developed in collaboration with Boston Pharmaceuticals following a licensing agreement. The first clinical trial of the new treatment is now underway in solid tumours, including aggressive triple negative breast cancers.
Currently, people with triple negative breast cancer receive taxane chemotherapies, such as paclitaxel, as their standard care. Paclitaxel also affects the distribution of chromosomes during cell division but blocks the cell from dividing, which causes the cell to die. However, some cells escape, becoming resistant to the drug and giving rise to more tumours.
Treatment with paclitaxel in combination with BOS172722 dramatically reduced time in cell division — from 110 minutes with paclitaxel alone to 15 minutes when combined with BOS172722. All cells treated with the combination divided with gross chromosomal abnormalities and died as a result, whereas 40% remained alive with paclitaxel alone. The MPS1 inhibitor was also effective at lower doses when used in combination with paclitaxel in mice, and was well tolerated by mice at the doses that almost completely eliminated the tumours.
“We have discovered a brand new type of cancer treatment that uses cancer’s rapid growth against it, by forcing cells through cell division so quickly that they accumulate fatal errors. The drug works especially well in combination with chemotherapy in triple negative breast cancer cells — the deadliest form of breast cancer, for which there are few successful treatments.
“Crucially, the combination is anticipated to be effective in cancer patients that have already become resistant to chemotherapy alone and has the potential to become a much-needed extra treatment option that could extend the lives of patients.”
Hope for the future
The drug’s development has been documented in the journal Molecular Cancer Therapeutics and was funded by ICR as well as Cancer Research UK, Breast Cancer Now and Sixth Element Capital. And while the phase I trial is not yet complete, the study authors believe the drug may go on to prove effective against other fast-growing cancers, including ovarian cancer.
“It’s really promising that combining this newly discovered drug with a standard chemotherapy could, in future, provide a new way to treat triple negative breast cancer and may even prevent the disease from becoming resistant to treatment,” said Baroness Delyth Morgan, Chief Executive at Breast Cancer Now.
“With triple negative breast cancer still lacking in targeted treatments, we urgently need to find new options to stop more women dying. This exciting study shows how well these drugs complement each other at a molecular level to destroy cancer cells.”
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