The drug is called BOS172722 and it forces cancer cells to multiply faster, which would seem to be counterintuitive. However, this faster cell division causes more fatal errors in the cells.
Researchers at The Institute of Cancer Research (ICR), London, identified a drug that appears to be effective in cancers that become resistant to chemotherapy. The drug is called BOS172722 and it forces cancer cells to multiply faster, which would seem to be counterintuitive. However, this faster cell division causes more fatal errors in the cells. And in the case of this drug, appears to cause fatal errors in all the cancer cells.
The research was published in the journal Molecular Cancer Therapeutics. It was funded by The Institute of Cancer Research (ICR) and Cancer Research UK, Breast Cancer Now and Sixth Element Capital LLP.
The drug has been effective in isolated cells and in laboratory mice. It is currently in a clinical trial in solid tumors, including aggressive triple-negative breast cancers. The research team also believes it might be effective in fast-growing cancers like ovarian cancer.
“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,” said Spiros Linardopoulos, Professor of Cancer Biology and Therapeutics at the ICR, who led the study. “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.”
The research team found that cancer cells grown in petri dishes typically went through cell division in 52 minutes. But when treated with the drug, which is an MPS1 inhibitor, the cancer cells underwent cell division in only 11 minutes.
MPS1 plays a primary role in controlling chromosome organization during cell division. It makes sure that chromosomes are properly distributed between daughter cells. When inhibited with the new drugs, the cancer cells sped through cell division and resulted in the wrong number of chromosomes, which lead to earlier cell death.
Patients with triple-negative breast cancer generally receive taxane chemotherapies, such as paclitaxel. Paclitaxel affects chromosome distribution during cell division but prevents cells from dividing—also resulting in cell death. However, some cells develop resistance to the drug.
Cancer cells receiving paclitaxel and BOS172722 decrease cell division from about 110 minutes with paclitaxel alone to 15 minutes. All the cells treated with the combination had gross chromosome abnormalities and died, compared to 40% surviving with paclitaxel alone.
The drug also worked at lower doses when used in combination with paclitaxel, at least in lab animals, and was well tolerated by the mice.
“Cancer’s ability to evolve and become drug resistant is the cause of the vast majority of deaths from the disease,” said Rajesh Chopra, director of Cancer Therapeutics in the new Centre for Cancer Drug Discovery. “We plan to counter that ability with the world’s first ‘Darwinian’ drug discovery program 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.”
