Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox.

Autor:	Kretzmann JA; Laboratory for Biomolecular Nanotechnology, Department of Physics, Technical University of Munich, Am Coulombwall 4a, 85748 Garching, Germany., Irving KL; School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia., Smith NM; School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia., Evans CW; School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
Jazyk:	angličtina
Zdroj:	NAR cancer [NAR Cancer] 2021 Dec 22; Vol. 3 (4), pp. zcab048. Date of Electronic Publication: 2021 Dec 22 (Print Publication: 2021).
DOI:	10.1093/narcan/zcab048
Abstrakt:	Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as 'undruggable', progress has been made in the development of small-molecule therapeutics to target relevant protein-protein, protein-DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers. (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.)
Databáze:	MEDLINE
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