A wedge is knocked out with a wedge
A group of scientists from the Institute of Cancer Research in London is testing the drug BOS172722, which can enhance the effect of chemotherapy for resistant cancer. It forces cancer cells to divide very quickly, which leads to fatal errors in DNA division.
A clinical trial of this treatment is currently underway, involving patients with solid tumors, including aggressive triple negative breast cancer. Researchers believe that it may also be effective in other rapidly growing tumors, such as ovarian cancer.
Mechanism of action
BOS172722 blocks MPS1 kinase in cancer cells, which plays a central role in controlling cell division. It participates in the organization of chromosomes during cell division, ensuring their proper distribution between daughter cells and making sure that cell division does not occur until they are evenly distributed.
Blocking MPS1 with BOS172722 leads to an acceleration of cell division with an incorrect distribution of chromosomes and, as a result, their death.
The researchers found that cancer cells treated with the MPS1 inhibitor performed division in just 11 minutes compared to 52 minutes without the drug.
It was noted that rapidly dividing cells of triple negative breast cancer, ovarian cancer and lung cancer were particularly sensitive to the effect of blocking MPS1.
Currently, people with triple negative breast cancer receive drugs from the group of taxanes (paclitaxel) as standard treatment. Paclitaxel also affects the distribution of chromosomes, but it blocks cell division, and this leads to its death. Over time, some cells become resistant to paclitaxel.
Paclitaxel therapy in combination with BOS172722 significantly reduced the time of cell division – from 110 minutes against the background of paclitaxel alone to 15 minutes when paclitaxel was combined with BOS172722. All cells treated with a combination of the two drugs were divided with gross chromosomal abnormalities and died, whereas 40% of the cells treated with paclitaxel alone remained alive.
The MPS1 inhibitor was also effective at lower doses when used in combination with paclitaxel in mice and was well tolerated by them at doses that almost completely eliminated the tumor.
Suppression of MPS1 activity is a qualitatively new type of cancer therapy that is able to "outwit" cancer by blocking the key evolutionary pathway – the rapid growth of cancer cells – against it, forcing cells to divide even faster and accumulate fatal genetic errors.
Phase I clinical trials of the combination of paclitaxel and BOS172722 are currently underway, and the oncology community is looking forward to the results.
Article by S. J. Anderhub et al. High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers published in the journal Molecular Cancer Therapeutics.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Institute of Cancer Research: New evolution-busting drug overcomes resistance in aggressive breast cancers.