Abstract PR008: Targeting mechanisms of dosage compensation to selectively kill aneuploid cancer cells

Abstract Aneuploidy is an abnormal chromosome composition and a general hallmark of human cancer. Aneuploidy causes detrimental cellular stresses, but cancer cells evolve to cope with these stresses. Consequently, targeting such mitigation mechanisms is a promising potential therapeutic strategy. As an abnormal dosage of gene products from altered chromosomes can cause RNA and proteotoxic stress, dosage compensation (DC) of imbalanced gene products was reported to mitigate these stresses in aneuploid cells. However, the mechanisms that regulate DC remain elusive. To address these mechanisms, we focused on the role(s) of stress granules (SGs) and RNA binding proteins (RBPs) in aneuploid cancer cells. Our recent study revealed that aneuploid cancer cells preferentially depend on RNA and protein metabolism, and need to attenuate translation in order to cope with proteotoxic stress (Ippolito 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr PR008.