Chromosomal instability and aneuploidy as causes of cancer drug resistance.

Lukow, Devon A, Sheltzer, Jason M (September 2021) Chromosomal instability and aneuploidy as causes of cancer drug resistance. Trends in Cancer. ISSN 2405-8033

DOI: 10.1016/j.trecan.2021.09.002


High levels of aneuploidy and chromosomal instability (CIN) are correlated with poor patient outcomes, though the mechanism(s) underlying this relationship have not been established. Recent evidence has demonstrated that chromosome copy number changes can function as point mutation-independent sources of drug resistance in cancer, which may partially explain this clinical association. CIN generates intratumoral heterogeneity in the form of gene dosage alterations, upon which the selective pressures induced by drug treatments can act. Thus, although CIN and aneuploidy impair cell fitness under most conditions, CIN can augment cellular adaptability, establishing CIN as a bet-hedging mechanism in tumor evolution. CIN may also endow cancers with unique vulnerabilities, which could be exploited therapeutically to achieve better patient outcomes.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL labs > Sheltzer lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 28 September 2021
Date Deposited: 11 Nov 2021 16:54
Last Modified: 21 Mar 2022 14:19
PMCID: PMC8933054

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