Report on the first SLFN11 monothematic workshop: from function to role as a biomarker in cancer

Abstract

SLFN11 is a recently discovered protein with a putative DNA/RNA helicase function. First identified in association with the maturation of thymocytes, SLFN11 was later causally associated, by two independent groups, with the resistance to DNA damaging agents such as topoisomerase I and II inhibitors, platinum compounds, and other alkylators, making it an attractive molecule for biomarker development. Later, SLFN11 was linked to antiviral response in human cells and interferon production, establishing a potential bond between immunity and chemotherapy. Recently, we demonstrated the potential role of SLN11 as a biomarker to predict sensitivity to the carboplatin/taxol combination in ovarian cancer. The present manuscript reports on the first international monothematic workshop on SLFN11. Several researchers from around the world, directly and actively involved in the discovery, functional characterization, and study of SLFN11 for its biomarker and medicinal properties gathered to share their views on the current knowledge advances concerning SLFN11. The aim of the manuscript is to summarize the authors’ interventions and the main take-home messages resulting from the workshop.

Predicting Tumor Response to Drugs based on Gene-Expression Biomarkers of Sensitivity Learned from Cancer Cell Lines

“…Among those drugs for which gene expression data can reasonably predict a cancer cell line's sensitivity, we identified many known drug-gene interactions as well as several novel associations. Our results are consistent with and lend additional support to the notion that the expression levels of ABCB1 and SLFN11 are potential biomarkers for cancer cell line sensitivity to multiple drugs (Ballestrero et al, 2017;Chen and Sikic, 2012;Pietanza et al, 2018;Vaidyanathan et al, 2016). Our results also revealed that SPRY2 expression is positively correlated with the sensitivity of the cancer cell lines to many MEK inhibitors from GDSC, suggesting that SPRY2 expression may be a predictive biomarker for the effectiveness of MEK kinase inhibitors.…”

Predicting Tumor Response to Drugs Based on Gene-expression Biomarkers of Sensitivity Learned From Cancer Cell Lines

“…are potential biomarkers for cancer cell line sensitivity to multiple drugs [30,[59][60][61]. Our results also revealed that SPRY2 expression is positively correlated with the sensitivity of the cancer cell lines to many MEK inhibitors from GDSC, suggesting that SPRY2 expression may be a predictive biomarker for the effectiveness of MEK kinase inhibitors.…”

Molecular genomic features associated with in vitro response of the NCI‐60 cancer cell line panel to natural products

“…to multiple categories of DNA-damaging antitumor agents including topoisomerase I and II inhibitors, PARP inhibitors, and platinum compounds in a variety of cancers[54][55][56][57][58][59][60][61][62].Figure S3shows the midpoint rooted hierarchical clustering [44] of 1302 natural products based on their log(GI50) values across the NCI-60 cell lines. Those compounds for which the sensitivity was significantly correlated with SLFN11 expression (FDR adjusted P < 0.05) are highlighted in yellow.…”