A new target for oncologists
Scientists have discovered the Achilles heel of cancer cells
Svetlana Maslova, Hi-tech+
An abnormal number of chromosomes in cancer cells can be a vulnerable cancer site. This unique characteristic of cancer cells has been known to researchers for a long time, but only now have they figured out how to use this knowledge against tumor progression. The research may lead to the development of fundamentally new drugs that will use this vulnerability to destroy cancer cells by blocking their division.
Article by Cohen-Sharir et al. Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition published in the journal Nature – VM.
Normal human cells contain two sets of 23 chromosomes each – one from the father and one from the mother. But aneuploid cells have a different number of chromosomes. When aneuploidy forms in cancer cells, the cells not only "carry" it, but can even contribute to the progression of the disease. The link between aneuploidy and cancer was discovered more than a century ago, long before it became known that cancer is a genetic disease, and even before the discovery of DNA as hereditary material. However, until now, research in this area has not yielded any important scientific results - researchers' understanding of how aneuploidy contributes to the development and spread of cancer has been limited. A new work by an international group of scientists has shown that cancer aneuploidy may be its Achilles heel.
Division of a normal cell (upper row) compared to a cell with an abnormally large number of chromosomes (lower row). From left to right: images obtained by laser confocal microscopy of DNA, mitotic spindle, kinesin-like protein KIF18A and all three components together. On the last panel, DNA is highlighted in green, and the spindle is red. The scale size (white) is 10 microns. Figure from the press release of the Technical University of Kaiserslautern Common weakness among cancers identified – VM.
It is estimated that approximately 90% of solid tumors, such as breast cancer and colon cancer, and 74% of blood cancers are aneuploid in nature. In the new work, advanced bioinformatics methods were used to quantify aneuploidy in approximately 1,000 cancer cell cultures. Then their genetic dependence and drug sensitivity were compared at low and high levels of aneuplodia.
It turned out that aneuploid cancer cells had an increased sensitivity to damage to the mitotic checkpoint, which ensures the correct separation of chromosomes during cell division, and also discovered the molecular basis of this process.
These results are important for the development of new drugs in personalized cancer therapy. For example, drugs that slow down the separation of chromosomes are already undergoing clinical trials, but their effectiveness has not yet been determined. But an equally important discovery is that it is now possible to use aneuplodia as a biomarker to identify patients who will benefit most from such therapy, the authors say.
"In order to apply the knowledge gained to the treatment of cancer patients, many more further studies will be required, but it is already clear that the results have important implications for medicine," concluded Uri Ben–David, the head of the work.
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