A team of researchers led by scientists from Tel Aviv University says they may have come across the “Achilles’ heel” of cancer cells, which could lead to the development of a whole new range of cancer drugs and treatments in the future.
Dr. Uri Ben-David of the Sackler Faculty 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 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 chromosome segregation occurs during cell division 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 characteristic of cancer cells. Not all cancers show aneuploidy, but about 90% of solid tumors and 75% of blood cancers, to some degree.
According to Ben-David, the findings offer a whole new way for medical research.
‘For decades we have been trying to understand why [aneuploidy] happens in cancer and how it contributes to the formation and progression of tumors, ”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 exploit this unique difference between cancer cells and normal cells to selectively kill the cancer cells.”
The study, published in the scientific journal Nature, the findings of which 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 general vision here is that it can be a very attractive way to selectively kill cancer cells by understanding how aneuploid cells differ from normal cells, and detecting the Achilles’ heel of aneuploid 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 looked in a laboratory using advanced bioinformatics methods to quantify their degree of aneuploidy, from most aneuploidy to least aneuploidy.
After determining the degree of chromosomal instability of the cancer cells, the scientists examined and compared their sensitivity with thousands of drugs.
Scientists have found that aneuploid cancer cells were extremely sensitive to the disorder of the mitotic control point – a so-called cellular mechanism that ensures the proper separation of chromosomes during cell division.
“This has enabled us to identify unique vulnerabilities of the aneuploid cells we have entered into and to characterize them in depth at the molecular and cellular level,” says Ben-David.
“We have found that if you inhibit the proteins of these pathways, the aneuploid cells are more sensitive to this interference than normal cells … so they are attractive targets for drug discovery and drug development.”
Illustrative. A cancer patient undergoing chemotherapy
(Photo: Shutterstock)
The research has important implications for future cancer treatments and personalized medicine. Currently, several drugs that inhibit or delay the separation of chromosomes are in clinical trials, but researchers have not been able to determine which patients would respond to them or not.
Ben-David’s study suggests that aneuploid scientists can help determine an individual’s response to these drugs.
Furthermore, these chromosomal abnormalities may also lead to the development of more effective cancer treatments in the future, as physicians may test for aneuploidy and treat accordingly.
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 runs Ben-David’s lab, calls the research groundbreaking.
“Aneuploidy is very, very difficult to study,” she says. “It affects so many genes at once.”
Cohen-Sharir emphasizes that the current study was conducted on cells in culture and not on actual tumors, and that further follow-up research should 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 using the unique properties of aneuploidy could eventually 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 put bleach on it 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 big breakthrough,” he says.