A team of researchers led by scientists at Tel Aviv University said they may have tripped over the “Achilles heel” of cancer cells, which may in the future lead to the development of an entirely new range of cancer drugs and treatments.
Dr. Uri Ben-David, from the Sackler Faculty of Medicine at Tel Aviv University, who led the research, says that scientists have known for more than a century that malignant cells have an abnormal number of chromosomes.
An image from the study led 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 do, to some extent.
According to Ben-David, the findings open an entirely new path for medical research.
“For decades, we have tried to understand why [aneuploidy] 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 been trying to see “whether we can take advantage of this unique difference between cancer cells and normal cells to selectively kill cancer cells”.
The study, which was published in the scientific journal Nature and whose findings were released Wednesday, was conducted in Ben-David’s 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 detecting the Achilles heel of aneuploid cells, this can 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, the researchers took about 1,000 cultures of cancer cells from patients and examined them in a laboratory using advanced bioinformatics methods to quantify their degree of aneuploidy, from the largest to aneuploidy.
After the degree of chromosomal instability of the cancer cells was verified, the scientists examined and compared their sensitivity to thousands of drugs.
Scientists found that aneuploid cancer cells were highly sensitive to mitotic checkpoint disturbance – a mechanism called the cell that ensures proper separation of chromosomes during cell division.
“This allowed us to identify unique vulnerabilities in the aneuploid cells that we analyzed and characterized in depth at the molecular and cellular level,” says Ben-David.
“We found that if you inhibit proteins in these pathways, aneuploid cells are more sensitive to this interference than normal cells … so they are attractive targets for drug discovery and development.”
Illustrative. A cancer patient undergoing chemotherapy
(Photo: Shutterstock)
The research has important implications for future cancer treatments and personalized medicine. At the moment, several drugs that inhibit or delay chromosome separation are in clinical trials, but the researchers were unable to identify which patients would respond to them or not.
Ben-David’s study suggests that aneuploidy may help scientists determine an individual’s response to these drugs.
In addition, the improvement of these chromosomal abnormalities could also lead to the development of more effective cancer treatments in the future, since doctors could test for aneuploidy and design an appropriate treatment.
Dr. Yael Cohen-Sharir, from the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University, is the lead author of the study. Cohen-Sharir, who manages Ben-David’s laboratory, considered the research innovative.
“Aneuploidy is very, very difficult to study,” she says. “It affects many genes at once.”
Cohen-Sharir emphasizes that the current study was carried out on cultured cells and not on actual tumors, and that more follow-up research needs to be done. The next step for researchers, she says, is to try to replicate the findings in mice.
Cancer cells
(Illustration: Tel Aviv University)
As for Ben-David, he is optimistic that taking advantage of the unique characteristics of aneuploidy could lead to the Holy Grail of cancer research: finding a way to kill malignant cells without harming healthy cells in the body.
“Killing cancer cells is very easy: you can pour bleach on 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 evaluated systematically in human cancer cells.
“That is why it is a major breakthrough,” he says.