Chemotherapy drugs like paclitaxel are the standard of care in triple-negative breast cancer, but some cancer cells easily escape the medicine, causing patients to become resistant to the treatment. Scientists at the Institute of Cancer Research (ICR) in London say they’ve found a way to prevent that escape—and it involves disrupting a key process in the evolution of cancer.
Cancer cells thrive by rapidly dividing. But if they divide too quickly, they can end up with errors in their DNA—specifically the wrong number of chromosomes. Those errors end up killing the cancer cells.
The ICR team used a drug from Boston Pharmaceuticals called BOS172722 to cause cancer cells to divide too rapidly. When combined with paclitaxel in lab dishes, all cancer cells died, while 40% of those treated with chemo alone survived. The combination treatment was also effective in mouse models of triple-negative breast cancer, the researchers reported in the journal Molecular Cancer Therapeutics.
A phase 1 trial testing the combination treatment in patients with solid tumors has started recruiting patients in the U.K.
BOS172722, which was discovered at ICR, works by blocking MPS1, a protein kinase that helps organize and distribute chromosomes during cell division. Without MPS1, cell division spins out of control. In fact, the ICR researchers observed that blocking MPS1 slashed the time it took for cells to divide from 110 minutes with paclitaxel alone to 15 minutes with the BOS172722 combo.
Hence, the drug “uses cancer's rapid growth against it, by forcing cells through cell division so quickly that they accumulate fatal errors,” said Spiros Linardopoulos, Ph.D., professor of cancer biology and therapeutics, in a statement. “Crucially, the combination is anticipated to be effective in cancer patients that have already become resistant to chemotherapy alone,” he added.
The ICR team tested the combination treatment in three mouse models of triple-negative breast cancer, including one in which the cancer had spread, primarily to the lungs. BOS172722 was well tolerated in combination with paclitaxel, they reported, and the combination produced a significant benefit in tumor shrinkage and survival at three months.
Boston Pharmaceuticals was launched in 2015 by pharma veteran Chris Viehbacher’s Gurnet Point, which put $600 million into the startup. Since then, it has nabbed several early-stage drugs as it works toward a goal of getting at least 20 assets into clinical trials. In 2018, for example, it picked up three anti-infectives from Novartis. It also acquired five drugs that GlaxoSmithKline shelved after Emma Walmsley took over as CEO.
BOS172722 is one of two oncology drugs listed in Boston Pharmaceuticals’ pipeline, which now includes nine clinical-stage programs and six preclinical drugs.
Triple-negative breast cancer is one of the toughest cancers to treat because of the lack of targeted drugs that are effective against this aggressive form of the disease. Several new approaches are being tried, including the gene-editing system CRISPR. In August, researchers at Boston Children's Hospital said they used CRISPR to knock out a key gene in triple-negative breast cancer, lipocalin 2, in mice, slowing tumor growth by 77%.
One potential advantage of BOS172722 is that it can be given orally, the ICR researchers noted in their study. And they believe ultimately the drug could hold promise in other fast-growing tumors, including ovarian cancer. The phase 1 trial will include about 68 patients and is estimated to be completed by the end of 2020.