Targeting vulnerabilities of aneuploid cells for cancer therapy

Aneuploidy is a common feature of cancer that drives tumor evolution, but it also creates cellular vulnerabilities that might be exploited therapeutically. Recent advances in genomic technologies and experimental models have uncovered diverse cellular consequences of aneuploidy, revealing dependencies on mitotic regulation, DNA replication and repair, proteostasis, metabolism, and immune interactions. Harnessing aneuploidy for precision oncology requires the combination of genomic, functional, and clinical studies that will enable translation of our improved understanding of aneuploidy to targeted therapies. In this review we discuss approaches to targeting both highly aneuploid cells and cells with specific common aneuploidies, summarize the biological underpinning of these aneuploidy-induced vulnerabilities, and explore their therapeutic implications.