A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers.
Bingnan ZhangKavya RamkumarRobert John CardnellCarl Michael GayC Allison StewartWei-Lien WangJunya FujimotoIgnacio I WistubaLauren Averett ByersPublished in: British journal of cancer (2021)
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.
Keyphrases
- dna damage
- papillary thyroid
- dna repair
- dna damage response
- immune response
- clinical trial
- oxidative stress
- squamous cell
- circulating tumor cells
- circulating tumor
- childhood cancer
- lymph node metastasis
- single molecule
- squamous cell carcinoma
- small molecule
- genome wide
- transcription factor
- cell free
- gene expression
- risk factors
- mesenchymal stem cells
- electronic health record
- stem cells
- cell therapy
- randomized controlled trial
- phase ii
- copy number
- ultrasound guided
- big data