Mechanistic vulnerabilities of genome instability in cancer
Two studies present converging evidence for a mechanism that drives genomic instability in cancer cells that are missing centrosome, and present potential avenues to exploit it therapeutically. Ross Chapman and colleagues, and Karen Oegema and colleagues, identify that amplification of TRIM37, a centrosome regulator, makes cancer cells more sensitive to centrosome depletion by PLK4 inhibition. Increased TRIM37 deregulates centrosome separation and can promote mitotic errors that lead to genomic instability, but also inhibits the formation of non-centrosomal foci that are required for cell division in centrosome-lacking cells. This can be targeted by inhibition of PLK4, which induces mitotic catastrophe.
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