Synergistic effect
Cancer drug is being developed without side effects for healthy cells
Researchers at the University of Geneva have discovered a new drug combination that is effective in fighting cancer cells without affecting healthy cells, according to a press release from New chemical weapon to combat cancer.
Article by Weiss et al. Identification of a Synergistic Multi-Drug Combination Active in Cancer Cells via the Prevention of Spindle Pole Clustering is published in the journal Cancers – VM.
The fight against cancer involves the destruction of cancer cells, but modern treatments inevitably have negative consequences for healthy cells. Patients often develop drug resistance and suffer side effects due to the doses used in the treatment. How can this double problem be solved? Scientists from the University of Geneva (UNIGE) (Switzerland) analyzed 200 combinations of various anticancer drugs in an attempt to reduce doses. They used a new technique to test the effects of the combination on cancer cells and healthy cells at the same time. Researchers have discovered a very promising mixture of four components, called C2, which can kill tumor cells, leaving healthy cells without damage.
Drugs that attack tumors must be aggressive to be effective. However, the balance between the destruction of cancer cells and the collateral damage inflicted on healthy cells is an ongoing problem. High doses of an anti-cancer drug can cause two main types of damage: progressive drug resistance as the body adapts to massive doses; and undesirable side effects on the patient's healthy cells. How then can we fight cancer without harming the patient? "The main goal is to reduce drug doses so that we can avoid resistance," explains Patricia Nowak–Slivinska, professor at the Institute of Pharmaceutical Sciences of Western Switzerland and UNIGE, as well as the University of Translational Research in the Field of Hematology (CRTOH). "That's why we are creating new formulas consisting of several low–dose drugs that will help us achieve our goal without causing any resistance."
UNIGE researchers focused on ten substances used to fight cancer and created about 200 possible combinations. "We used a method that we developed in our laboratory to simultaneously test these different combinations in vitro on a cancer cell and on a healthy cell. The goal was to directly compare the effect of treatment on two types of cells," continues Professor Novak-Slivinska. "We were able to exclude formulas that did not destroy diseased cells, as well as formulas that affected healthy cells."
Thanks to this method of simultaneous verification, UNIGE researchers have identified the most effective combinations with the least possible side effect on healthy cells, especially by isolating one of them: C2.
C2, which consists of four products (tubacin, CI-994, erlotinib and dasatinib), has a new and very promising mechanism of action. "During our in vitro tests, we found that C2 kills 20 times more cancer cells than other combinations, while keeping healthy cells safe," explains Patrick Meraldi, professor of Cell Physiology and Metabolism at the UNIGE and CRTOH Faculty of Medicine.
The peculiarity of C2 is that it targets only additional cell centers in tumor cells. "Each cell is equipped with two centrosomes – organelles that allow it to divide into two parts, pulling each half of the cell," explains Professor Meraldi. As for cancer cells, they have more centrosomes that pull the cell in three or four directions during its division, which leads to cell death. To prevent this, cancer cells group centrosomes into two poles. "C2 blocks this grouping, causing cell death specific to tumor cells with additional centrosomes, leaving healthy cells without damage," continues the researcher from Geneva.
Currently, there is a drug on the market that also causes separation in three or four directions: paclitaxel. But it needs to be taken in a large dosage, which causes numerous side effects in patients. "That's why we want to replace the use of paclitaxel with C2 or a combination of both, which will reduce the risk of resistance and toxicity," says Professor Novak-Slivinska. To do this, UNIGE researchers have filed a patent for the C2 combination and are currently at the stage of in vivo testing on mice so that they can observe the effect of this new formula on the whole body, not just on an isolated cell.
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