Chromosome Missegregation as a Modulator of Radiation Sensitivity.

Autor: Cosper PF; Department of Human Oncology, Madison, WI; University of Wisconsin Carbone Cancer Center, Madison, WI., Copeland SE; Molecular & Cellular Pharmacology Graduate Training Program, Madison, WI., Tucker JB; Cancer Biology Graduate Training Program, Madison, WI., Weaver BA; University of Wisconsin Carbone Cancer Center, Madison, WI; Department of Cellular and Regenerative Biology, Madison, WI; Department of Oncology/McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI.. Electronic address: baweaver@wisc.edu.
Jazyk: angličtina
Zdroj: Seminars in radiation oncology [Semin Radiat Oncol] 2022 Jan; Vol. 32 (1), pp. 54-63.
DOI: 10.1016/j.semradonc.2021.09.002
Abstrakt: Chromosome missegregation over the course of multiple cell divisions, termed chromosomal instability (CIN), is a hallmark of cancer. Multiple causes of CIN have been identified, including defects in the mitotic checkpoint, altered kinetochore-microtubule dynamics, centrosome amplification, and ionizing radiation. Here we review the types, mechanisms, and cellular implications of CIN. We discuss the evidence that CIN can promote tumors, suppress them, or do neither, depending on the rates of chromosome missegregration and the cellular context. Very high rates of chromosome missegregation lead to cell death due to loss of essential chromosomes; thus elevating CIN above a tolerable threshold provides a mechanistic opportunity to promote cancer cell death. Lethal rates of CIN can be achieved by a single insult or through a combination of insults. Because ionizing radiation induces CIN, additional therapies that increase CIN may serve as useful modulators of radiation sensitivity. Ultimately, quantifying the intrinsic CIN in a tumor and modulating this level pharmacologically as well as with radiation may allow for a more rational, personalized radiation therapy prescription, thereby decreasing side effects and increasing local control.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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