5 October 2019
A new type of drug that blocks one of cancer’s escape routes from chemotherapy could be used to treat aggressive breast cancers, scientists at The Institute of Cancer Research, London have found.
The study, part-funded by Breast Cancer Now, found that the drug could reinvigorate the response to chemotherapy in cancers that had become resistant, in both cells grown in the lab and in mice.
The drug, known as BOS172722, works by forcing cancer cells through cell division too quickly, leading to fatal errors in parcelling out DNA.
The first clinical trial of the new treatment is now under way in solid tumours including triple-negative breast cancers, and the researchers believe it might also be effective against other fast-growing cancers including ovarian cancer.
The drug blocks a molecule called MPS1, which plays a central role in controlling how cells split into two, making daughter cells. MPS1 is involved in organisation of DNA during this process, ensuring it is distributed correctly between the two daughter cells. It also makes sure that a cell doesn’t split into two until the DNA has been parcelled out evenly.
By blocking MPS1 using the new drug, cancer cells speed through this process and die as a consequence.
The researchers found that cancer cells in dishes treated with the MPS1 drug went through cell division in just 11 minutes, compared with 52 minutes without the drug.
And cells from triple-negative breast cancers, ovarian and lung cancers, were especially sensitive to the effects of blocking MPS1.
Currently, people with triple-negative breast cancer receive chemotherapies, such as paclitaxel, as their standard care. Paclitaxel also interferes with the way cells split into two. However, some cancer cells escape becoming resistant to the drug and giving rise to more tumours.
Treatment with paclitaxel in combination with BOS172722 dramatically reduced the time it took cancer cells to divide — from 110 minutes with paclitaxel alone to 15 minutes when combined with BOS172722. All cells treated with the combination died as a result, whereas 40 per cent remained alive with paclitaxel alone.
The MPS1 drug 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.
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which helped to fund the study, said:
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.
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.
We now look forward to the results of clinical trials to understand whether this approach may be as effective and safe in humans. In the meantime, anyone with questions about their breast cancer treatment can call our free Helpline on 0808 800 6000 to speak to one of our expert nurses.
Professor Spiros Linardopoulos, Professor of Cancer Biology and Therapeutics at The Institute of Cancer Research, London who led the study, said:
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.
The phase I trial of this combination is currently well under way and I look forward to the results.
Professor Rajesh Chopra, Director of Cancer Therapeutics in the new Centre for Cancer Drug Discovery, said:
Cancer’s ability to evolve and become drug resistant is the cause of the vast majority of deaths from the disease. We plan to counter that ability with the world’s first ‘Darwinian’ drug discovery programme within our Centre for Cancer Drug Discovery, dedicated to creating a new generation of anti-evolution treatments.
Our new MPS1 inhibitor is a great example of a drug that seeks to outsmart cancer by blocking off a key evolutionary escape route, and in doing so we believe it can breathe new life into a chemotherapy that had ceased to be effective.
The new study is published in the journal Molecular Cancer Therapeutics and was funded by The Institute of Cancer Research (ICR), Cancer Research UK, Breast Cancer Now and Sixth Element Capital LLP.