Sayak Banerjee, Amity University Kolkata
Multiple genetic changes direct cancer from mutations to aneuploidy. Aneuploidy is the presence of an unusual number of chromosomes in cancer cells. It is estimated that inherently, 90% of solid tumors, like breast cancer and colon cancer, and 75% of blood cancers are caused by aneuploidy. Although being an indication of cancer, the apprehension of the same is limited. A new study from Tel Aviv University (TAU) illustrates how this attribute of cancer cells can be observed as a weak link, hence potentially leading to the development of drugs that kill cancer cells.
Selective targeting of aneuploid cells is an enticing strategy for cancer treatment. Nonetheless, it is uncertain whether aneuploidy renders any vulnerabilities in cancer cells. The researchers mapped the aneuploidy landscapes of around 1,000 human cancer cell lines. These were then used to compare the genetic dependency and drug sensitivity between the cells with a high level of aneuploidy and the cells with a low level of aneuploidy. Their data revealed the enhanced sensitivity of cancer cells and their molecular basis towards the damage to the mitotic checkpoint.
They stated that aneuploid cancer cells became more and more sensitive to inhibition of Spindle Assembly Checkpoint (SAC) with time, thus exhibiting abnormal spindle geometry and dynamics. As the SAC was inhibited, they kept dividing, leading to the aggregation of mitotic defects, giving rise to unstable and incompatible karyotypes. On that account, aneuploid cancer cells despite overcoming inhibition of SAC more promptly than diploid cells, their long-term proliferation was compromised.
These data indicate that aneuploidy can likely be used as a biomarker to distinguish patients who will respond better to the drugs that target the delay of separating chromosomes. For the treatment to be implemented on cancer patients many more studies must be analyzed, and these studies could have several medical implications.
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Source: Cohen-Sharir, Y., McFarland, J.M., Abdusamad, M. et al. Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition. Nature (2021). https://doi.org/10.1038/s41586-020-03114-6
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