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A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers.

Authors :
Zhang, Bingnan
Ramkumar, Kavya
Cardnell, Robert John
Gay, Carl Michael
Stewart, C. Allison
Wang, Wei-Lien
Fujimoto, Junya
Wistuba, Ignacio I.
Byers, Lauren Averett
Source :
British Journal of Cancer; Nov2021, Vol. 125 Issue 10, p1333-1340, 8p
Publication Year :
2021

Abstract

DNA-damaging agents exploit increased genomic instability, a hallmark of cancer. Recently, inhibitors targeting the DNA damage response (DDR) pathways, such as PARP inhibitors, have also shown promising therapeutic potential. However, not all tumors respond well to these treatments, suggesting additional determinants of response are required. Schlafen 11 (SLFN11), a putative DNA/RNA helicase that induces irreversible replication block, is emerging as an important regulator of cellular response to DNA damage. Preclinical and emerging clinical trial data suggest that SLFN11 is a predictive biomarker of response to a wide range of therapeutics that cause DNA damage including platinum salts and topoisomerase I/II inhibitors, as well as PARP inhibitors, which has raised exciting possibilities for its clinical application. In this article, we review the function, prevalence, and clinical testing of SLFN11 in tumor biopsy samples and circulating tumor cells. We discuss mounting evidence of SLFN11 as a key predictive biomarker for a wide range of cancer therapeutics and as a prognostic marker across several cancer types. Furthermore, we discuss emerging areas of investigation such as epigenetic reactivation of SLFN11 and its role in activating immune response. We then provide perspectives on open questions and future directions in studying this important biomarker. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
125
Issue :
10
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
153454702
Full Text :
https://doi.org/10.1038/s41416-021-01476-w