A CINful way to overcome addiction: how chromosomal instability enables cancer to overcome its oncogene addiction.

Autor: Bronder D; Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Bakhoum SF; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2020 Mar 06; Vol. 12 (3), pp. e12017. Date of Electronic Publication: 2020 Feb 18.
DOI: 10.15252/emmm.202012017
Abstrakt: Oncogene-addicted tumors present a valuable target for therapeutic intervention and an opportunity to achieve a wide therapeutic window. Nonetheless, resistance to targeted therapies is frequently observed and it arises through multiple mechanisms, including mutations in the target gene. Chromosomal instability, a defining feature of human cancer, has been linked to targeted therapy resistance, but the mechanism underlying this association is poorly understood. In the current issue of EMBO Molecular Medicine, Salgueiro et al show that chromosomal instability can lead to the generation of alternative oncogenic drivers, thereby providing the ability for cancer cells to overcome the oncogene withdrawal bottleneck. Importantly, this study shows that, by generating de novo genomic diversity, chromosomal instability serves as an adaptive response to therapeutic insult.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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