Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response
Willis SE., Winkler C., Roudier MP., Baird T., Marco-Casanova P., Jones EV., Rowe P., Rodriguez-Canales J., Angell HK., Ng FSL., Waring PM., Hodgson D., Ledermann JA., Weberpals JI., Dean E., Harrington EA., Barrett JC., Pierce AJ., Leo E., Jones GN.
Schlafen 11 (SLFN11) is a gene encoding for a protein involved in the irreversible arrest of cell replication under DNA-damaging stress. SLFN11 is expressed differently across various cancers. When overexpressed, SLFN11 inhibits tumor replication and growth by early recruitment to stressed replication forks, making tumors more sensitive to a range of anti-cancer treatments, including topoisomerase I–II inhibitors, DNA alkylating agents, platinum salts, anti-metabolites, anti-tumor antibiotics, poly ADP-ribose polymerase (PARP) inhibitors and immunotherapies. SLFN11 expression can be silenced in cancer cells through different epigenetic mechanisms, resulting in SLFN11 downregulation and resistance to anti-cancer treatments. In this context, SLFN11 is increasingly being recognized as a promising biomarker for predicting cancer treatment responses. Its expression levels can inform clinical decisions, helping to identify patients most likely to benefit from therapies that exploit replication stress and to select new drug combinations that specifically aim to overcome SLFN11 deficiency.