Health
Characteristics of cancer revealed to be a tragic defect
Cancer is caused by multiple genetic changes, from mutations to aneuploidies. Aneuploidy is the presence of an abnormal number of chromosomes in cancer cells. Aneuploidy is a hallmark of cancer, but its understanding is limited. However, a new study from Tel Aviv University (TAU) shows how this feature of cancer cells is now considered a weakness and may lead to the development of drugs that kill cancer cells.
Studies recently published in the journal Nature In a treatise titled “”Aneuploidy makes cancer cells vulnerable to mitotic checkpoint inhibition.Was conducted in the laboratory of Dr. Uri Ben-David, an assistant professor at TAU’s Sackler School of Medicine, in collaboration with six laboratories in four other countries.
“Selective targeting of aneuploid cells is an attractive strategy for cancer treatment,” the researchers write. “But it is unclear whether aneuploidy creates clinically relevant vulnerabilities in cancer cells. Here, we map the aneuploidy status of about 1,000 human cancer cell lines, genetically and chemically. We analyzed the perturbation screen to identify cell vulnerabilities associated with aneuploidy. “
According to Ben-David, aneuploidy is the most common genetic change in cancer. About 90% of solid tumors such as breast and colon cancers, and 75% of blood cancers are aneuploidy in nature. Researchers used advanced bioinformatics techniques to quantify aneuploidy in approximately 1,000 cancer cell cultures. Next, the researchers compared the genetic dependence and drug susceptibility of cells with high levels of aneuploidy with those of cells with low levels of aneuploidy.
Their findings reveal increased susceptibility of cancer cells to damage to mitotic checkpoints. They also discovered the molecular basis for increasing the sensitivity of aneuploid cancer cells.
“In fact, aneuploid cancer cells have become more and more sensitive to inhibition of SAC over time,” the researchers say. “Aneuploid cells show abnormal mitotic spindle shape and dynamics, continue to divide when SAC is inhibited, accumulate mitotic defects, and become an unstable and incompatible karyotype. Therefore, aneuploid cancer cells were able to overcome inhibition of SAC more easily than diploid cells, but their long-term growth was at risk.
Drugs that target delayed chromosome segregation are in clinical trials, but it is unclear which patients respond to them and which do not. These findings suggest that it may be possible to use aneuploidy as a biological marker to identify patients who respond better to these drugs.
“It should be emphasized that this study was performed on cells in culture, not on cancer patients. More follow-up needs should be undertaken to translate it into treatment for cancer patients. Still, even at this stage, it is clear that this study can have many medical implications, “said Ben David.
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