New drug may quash chemotherapy resistance in aggressive breast cancers
Treating women with aggressive breast cancers may be possible, thanks to a new drug discovered by scientists at The Institute of Cancer Research, London. Of the estimated 1-1.3 billion women diagnosed with breast cancer annually, around 15-20 percent have a form of breast cancer - called Triple Negative Breast Cancer (TNBC) - that do not respond to usual treatments such as hormonal therapy and targeted therapy against a protein called Human Epidermal Growth Factor Receptor HER2. TNBC is considered a long-lasting orphan disease, given the minimal progress made in identifying therapeutics over the past several decades.
To target such aggressive cancer forms, scientists have tested a drug, BOS172722, in cultured cells in the lab and in mice. The drug was designed to block the action of MPS 1, a molecule that plays a crucial role in cell division. Without MPS 1, chromosomes don’t get distributed accurately between the two dividing cells.
"We and others have shown that MPS1 expression is elevated in this type of cancer. TNBC cell lines were more sensitive to MPS1 inhibition in comparison to luminal [hormone sensitive] types of breast cancer. Therefore, we initiated a program to discover MPS1 inhibitors to treat this disease", said Spiros Linardopoulos, Professor of Cancer Biology and Therapeutics at The Institute of Cancer Research, London.
By inhibiting this molecule, they observed that cell division in cancer cells growing in the lab speeds up: the cells took just under 11 minutes to complete one division, as opposed to 52 minutes under normal conditions. At this speed, cancer cells make costly mistakes, a consequence of which leads to cell death, as each diving cell receives a wrong number of chromosomes.
“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 TNBC – the deadliest form of breast cancer for which there are few successful treatments", said Prof Linardopoulos, in a statement.
However, according to him, testing the drug in the lab and later in mice showed results that were consistent with a commonly used drug to TNBC: paclitaxel. It attacks cancer cells in a manner similar to that of the test drug, albeit some cells escape and give rise to new tumors.
So the team decided to use a combinational approach. By combining with paclitaxel with the test drug, the researchers observed that the cell could divide in 15 minutes. They also showed that all cells with an abnormality in chromosome number died, while 60 percent of their counterparts treated with paclitaxel alone, died. Linardopoulos added, "The combination showed significant regression of the tumours [in mice] even at several weeks after the last treatment."
Their results are promising. So the team of scientists are already working on the next step: testing the combination drug in humans. The drug is currently undergoing its first clinical trial. It is being tested in patients with solid tumors, including triple negative breast cancer, read the press statement. They add that the drug may treat ovarian cancer, too. The team is currently assessing the Maximum Tolerated Doses (MTD) of the combination drug in patients with different cancers.