A team of researchers led by scientists at Tel Aviv University say they may have run into the “Achilles heel” of cancer cells, which in the future could lead to the development of a completely new range of drugs and cancer treatments.
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 the study conducted by Tel Aviv University that found a weakness in cancer cells
(Image: Tel Aviv University)
Humans have 46 chromosomes (two groups of 23), but in cancer this number changes because, during cell division, chromosomal segregation occurs that 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 avenue for medical research.
“For decades we have been trying to understand why [aneuploidy] it happens in cancer and how it contributes to tumor formation and progression, ”says Ben-David.
Dr. Show 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, published in the scientific journal Nature and whose findings were published Wednesday, was conducted in Ben-David’s lab at Tel Aviv University in collaboration with six labs in four other countries: the United States, Germany, the Netherlands and Italy.
“The overview here is that if we understand how aneuploid cells are different from normal cells and detect 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
(Photo: Shutterstock)
In the study, researchers took about 1,000 cancer cell cultures from patients and examined them in a laboratory using advanced bioinformatics methods in order to quantify their degree of aneuploidy, from most aneuploidy. to the minimum aneuploidy.
After ascertaining the degree of chromosomal instability of the cancer cells, the scientists examined and compared their sensitivity with thousands of drugs.
The scientists found that aneuploid cancer cells were very sensitive to disruption of the mitotic control point, a mechanism called cellular that ensures proper separation of chromosomes during cell division.
“This allowed us to identify unique vulnerabilities in the aneuploid cells that we continued and that we characterized in depth at the molecular and cellular level,” says Ben-David.
“We have found that if you inhibit proteins from these pathways, aneuploid cells are more sensitive to this interference than normal cells … therefore, they are attractive targets for drug discovery and development.”
Illustrative. An oncology patient undergoing chemotherapy
(Photo: Shutterstock)
Research has important implications for future cancer treatments and personalized medicine. At present, there are several drugs that inhibit or delay the separation of chromosomes in clinical trials, but researchers have not been able to identify which patients would respond or not.
Ben-David’s study suggests that aneuploidy could help scientists determine an individual’s response to these drugs.
In addition, perfecting these chromosomal abnormalities could also lead to the development of more effective cancer treatments in the future, as physicians could test for aneuploidy and develop treatment accordingly.
Dr. Yael Cohen-Sharir, of 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, said the research was innovative.
“Aneuploidy is very, very difficult to study,” he says. “It affects so many genes at once.”
Cohen-Sharir stresses that the current study was conducted on cells in culture and not on actual tumors, and that more follow-up research is needed. According to her, the next step for researchers 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 can lead to Holy Grail research into cancer: finding a way to kill malignant cells without damaging healthy cells. cos.
“Killing cancer cells is very easy: you can pour bleach on them and they will die, but the hardest part is doing it without killing normal cells,” he says.
Ben-David says that, as far as he knows, this is the first time aneuploidy has been systematically analyzed in human cancer cells.
“That’s why it’s a breakthrough,” he says.