Called BOS172722, this new type of drug blocks one of the leading cancer-modifying escape routes, paving the way for its use in chemotherapy to treat aggressive triple-negative breast cancers.
The most common and deadliest cancer in women, breast cancer is diagnosed every year in more 250,000 new patients in the United States and causes more 40,000 deaths according to the CDC, based on 2016 data.
As Pink October begins, which aims to raise awareness about breast cancer screening and raise funds for research, a new study by researchers at the Institute of Cancer Research in London is rather encouraging. In the journal Molecular Cancer Therapeutics, the researchers explain having discovered a new type of drug that can make chemotherapy more effective in cases of resistant breast cancers.
Already tested successfully in the laboratory and on mice, this new drug called BOS172722 is now the subject of a first clinical trial on solid tumors, including aggressive triple-negative breast cancers, that is to say without no known marker on the surface of the cancer cells, likely to respond to targeted therapy.
The specificity of BOS172722 is that it blocks a molecule called MPS1, which plays a central role in the control of cell division. By forcing the cancer cells to divide too quickly, this leads to fatal errors in the fragmentation of their DNA.
The researchers found that cancer cells with the MPS1 inhibitor underwent cell division in just 11 minutes, compared to 52 minutes without the drug. However, they also found that the rapidly dividing cells derived from triple-negative breast cancers, but also from ovarian and lung cancers, were particularly sensitive to the effects of MPS1 blockade.
Currently, people with triple-negative breast cancer receive taxane chemotherapy, such as paclitaxel, as a standard treatment. While paclitaxel affects the distribution of chromosomes during cell division and prevents the cell from dividing, resulting in the death of the cancer cells, some of the cancerous cells have however developed resistance and give rise to other tumors.
However, when paclitaxel treatment is combined with BOS172722, the cell division time is significantly reduced from 110 minutes with paclitaxel alone to 15 minutes in combination with BOS172722. All cells treated with the combination showed macroscopic chromosomal abnormalities and died, while 40% remained alive with paclitaxel alone.
According to the researchers, this MPS1 inhibitor was also effective at lower doses when used in combination with paclitaxel in mice. It was also well tolerated by the mouse at doses that almost completely eliminated the tumors.
“We have discovered a whole new type of cancer treatment that uses the rapid growth of cancer against it, forcing cells to break through cell division so quickly that they accumulate fatal errors. The drug works particularly well in combination with the chemotherapy in triple-negative breast cancer cells – the most lethal form of breast cancer for which there are few effective treatments,” says Professor Spiros Linardopoulos, professor of biology and cancer therapeutics at the Institute of Cancer Research of London, who led the study.
According to professor Linardopoulos, the drug BOS172722 “has the potential to become a very necessary additional therapeutic option that could extend the life of patients” with triple-negative breast cancer. “The phase I trial of this combination is underway and I am looking forward to the results,” he concludes.