Targeting the Adaptability of Heterogeneous Aneuploids
| Autor: | Rong Li, Scott McCroskey, William D. Bradford, Wahid A. Mulla, Boris Rubinstein, Judith Berman, Hung-Ji Tsai, Juliana Conkright, Jeffrey S. Haug, Lauren Weems, Chris Seidel, Andrei Kucharavy, Guangbo Chen |
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| Přispěvatelé: | Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular & Cellular Biology - University of Minnesota, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Tsinghua University [Beijing] (THU), NIH [RO1GM059964], Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2015 |
| Předmět: |
Antifungal Agents
[SDV]Life Sciences [q-bio] media_common.quotation_subject Population Aneuploidy Saccharomyces cerevisiae Computational biology Irinotecan Genome Article General Biochemistry Genetics and Molecular Biology Adaptability 03 medical and health sciences 0302 clinical medicine Drug Resistance Fungal Cell Line Tumor Candida albicans medicine Humans education Fluconazole 030304 developmental biology media_common Genetics 0303 health sciences education.field_of_study biology Biochemistry Genetics and Molecular Biology(all) Karyotype medicine.disease biology.organism_classification Antineoplastic Agents Phytogenic ErbB Receptors Evolvability Drug Resistance Neoplasm 030220 oncology & carcinogenesis Pharmacogenomics Camptothecin Hygromycin B Glioblastoma |
| Zdroj: | Cell Cell, 2015, 160 (4), pp.771-784. ⟨10.1016/j.cell.2015.01.026⟩ Cell, Elsevier, 2015, 160 (4), pp.771-784. ⟨10.1016/j.cell.2015.01.026⟩ |
| ISSN: | 0092-8674 1097-4172 |
| DOI: | 10.1016/j.cell.2015.01.026 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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