Skip to Main content Skip to Navigation
Journal articles

Targeting the Adaptability of Heterogeneous Aneuploids

Abstract : Aneuploid genomes, characterized by unbalanced chromosome stoichiometry (karyotype), are associated with cancer malignancy and drug resistance of pathogenic fungi. The phenotypic diversity resulting from karyotypic diversity endows the cell population with superior adaptability. We show here, using a combination of experimental data and a general stochastic model, that the degree of phenotypic variation, thus evolvability, escalates with the degree of overall growth suppression. Such scaling likely explains the challenge of treating aneuploidy diseases with a single stress-inducing agent. Instead, we propose the design of an ``evolutionary trap'' (ET) targeting both karyotypic diversity and fitness. This strategy entails a selective condition ``channeling'' a karyotypically divergent population into one with a predominant and predictably drugable karyotypic feature. We provide a proof-of-principle case in budding yeast and demonstrate the potential efficacy of this strategy toward aneuploidy-based azole resistance in Candida albicans. By analyzing existing pharmacogenomics data, we propose the potential design of an ET against glioblastoma.
Document type :
Journal articles
Complete list of metadata
Contributor : HAL Sorbonne Université Administateur Connect in order to contact the contributor
Submitted on : Monday, May 29, 2017 - 11:25:18 AM
Last modification on : Sunday, June 26, 2022 - 10:01:12 AM

Links full text



Guangbo Chen, Wahid A. Mulla, Andrei Kucharavy, Hung-Ji Tsai, Boris Rubinstein, et al.. Targeting the Adaptability of Heterogeneous Aneuploids. Cell, Elsevier, 2015, 160 (4), pp.771-784. ⟨10.1016/j.cell.2015.01.026⟩. ⟨hal-01528517⟩



Record views