A team of researchers led by scientists at Tel Aviv University says they may have come across the “Achilles’ heel” of cancer cells, which could lead to the development of a completely new range of drugs and treatments in the future. cancer.
Dr. Uri Ben-David of the Sackler School of Medicine at Tel Aviv University, who led the research, says scientists have known for more than a century that malignant cells have an abnormal number of chromosomes.
An image from a study conducted by Tel Aviv University that found a weakness in cancer cells
(Image: Tel Aviv University)
Humans have 46 chromosomes (two sets of 23), but in cancer this number changes because, during cell division, chromosomal segregation occurs which can lead to a phenomenon called aneuploidy.
Aneuploidy, the presence of an abnormal number of chromosomes in a cell, not only causes common genetic disorders, but is also a hallmark of cancer cells. Not all cancers have aneuploidy, but about 90% of solid tumors and 75% of blood cancers to some extent.
According to Ben-David, the findings open a whole new path for medical research.
“We have been trying to understand why for decades [aneuploidy] it happens in cancer and how it contributes to the formation and progression of the tumor, ”says Ben-David.
Dr. Uri Ben-David
(Photo: Tel Aviv University)
More importantly, says Ben-David, scientists have tried to see “whether we can take advantage of this rather unique difference between cancer cells and normal cells to selectively destroy cancer cells.”
The study, which was published in the scientific journal Nature and whose findings were published Wednesday, was conducted in the Ben-David laboratory at Tel Aviv University in collaboration with six laboratories in four other countries – the United States, Germany, the Netherlands and Italy. .
The overview here is that by understanding how aneuploid cells are different from normal cells and by detecting the Achilles heel of aneuploid cells, this could be a very attractive way to selectively kill cancer cells, says Ben-David.
Illustrative. A cancer patient undergoes an MRI scan
(Photo: Shutterstock)
In the study, researchers took approximately 1,000 cancer cell cultures from patients and analyzed them in a laboratory using advanced bioinformatics methods to quantify their degree of aneuploidy, from the largest aneuploidy to the smallest aneuploidy.
After determining the degree of chromosomal instability of cancer cells, the scientists then examined and compared their sensitivity with thousands of drugs.
The scientists found that aneuploid cancer cells were extremely sensitive to disruption of the mitotic control point – a so-called cellular mechanism that ensures the correct separation of chromosomes during cell division.
“This allowed us to identify the unique vulnerabilities of aneuploid cells that we continued and characterized in depth at the molecular and cellular level,” says Ben-David.
We found that if you inhibit the proteins in these pathways, aneuploid cells are more sensitive to this interference than normal cells … therefore, they make attractive targets for the discovery and development of drugs. ”
Illustrative. A cancer patient undergoing chemotherapy
(Photo: Shutterstock)
Research has important implications for future treatments for cancer and personalized medicine. At present, several drugs that inhibit or delay chromosome separation are in clinical trials, but researchers have not been able to identify patients who would respond or not.
Ben-David’s study suggests that aneuploidy may help scientists determine an individual’s response to these drugs.
Moreover, the improvement of these chromosomal abnormalities could also lead to the development of more effective treatments against cancer in the future, as doctors could test for aneuploidy and treat accordingly.
Dr. Yael Cohen-Sharir, of Tel Aviv University’s Department of Human Molecular Genetics and Biochemistry, is the lead author of the study. Cohen-Sharir, who runs Ben-David’s lab, called the research revolutionary.
“Aneuploidy is very, very difficult to study,” she says. “It affects so many genes at once.”
Cohen-Sharir points out that the current study was performed on cells in culture and not on real tumors and that further research needs to be done. The next step for researchers, she says, is to try to replicate the findings on mice.
Cancer cells
(Illustration: Tel Aviv University)
As for Ben-David, he is optimistic that capitalizing on the unique features of aneuploidy could eventually lead to the Holy Grail of cancer research: finding a way to kill malignant cells without affecting healthy cells in the body.
“Killing cancer cells is very easy: you can bleach them and they will die, but the hard part is doing it without killing normal cells,” he says.
Ben-David says that, as far as he knows, this is the first time that aneuploidy has been systematically evaluated in human cancer cells.
“That’s why it’s a major breakthrough,” he says.