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SLFN11 underexpression

Other names: SLFN11, Schlafen Family Member 11,SLFN8/9
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High SLFN11 expression correlates with sensitivity to lurbinectedin in small cell lung cancer (SCLC) models (AACR 2023)
Schlafen 11 (SLFN11), a putative DNA/RNA helicase irreversibly binds to DNA replication forks resulting in replication block and is a predictive biomarker of response to therapeutics that elicit DNA damage including cisplatin, topoisomerase I/II inhibitors and PARP inhibitors.Objective: Evaluate the role of SLFN11 expression in predicting response to lurbinectedin, a DNA damaging agent, in human SCLC cell lines and in vivo models. Cytotoxicity assays: SCLC cell lines DMS 53, DMS 114, NCI-H69, NCI-H82, NCI-H196, NCI-H209, NCI-H211, NCI-H446, NCI-H526, NCI-H841, NCI-H889, NCI-H1048, and SHP-77 were tested with lurbinectedin dose range from 100 nM to 0.01 nM. Cell viability assays in 13 SCLC models confirm high SLFN11 expressing cell lines are 4-fold more sensitive to lurbinectedin compared to low SLFN11 expressing cell lines (ΔpIC50 = 0.64; p = 0.0451). The in vivo efficacy data confirms that the SLFN11 high NCI-H1048 model is more responsive with 90% TGI compared to 35% observed in SLFN11 low models (NCI-H889 and NCI-H69) at the highest lurbinectedin dose (p-value = 0.006). Efficacy data confirms correlation to SLFN11 protein expression, consistent with the RNA level association.
PARP Biomarker
SLFN11 (Schlafen Family Member 11)
SLFN11 expression • SLFN11 overexpression • SLFN11 underexpression
cisplatin • Zepzelca (lurbinectedin)
Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery in Glioblastoma. (PubMed, Cancer Res)
Conversely, low SLFN11 expression rendered GSCs susceptible to the oncolytic flavivirus Zika. This discovery effort based upon ASE revealed novel points of vulnerability in GSCs, suggesting a potential alternative treatment strategy for chemotherapy resistant glioblastoma.
Journal • PARP Biomarker
SLFN11 (Schlafen Family Member 11)
SLFN11 expression • SLFN11 underexpression