Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer

Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer

Wijdeven R, 2015, Cancer Research (Link to abstract)


The authors created a panel of knockout haploid cells using CRISPR and tested them systematically to identify gene products related to resistance to topoisomerase II inhibitors. They confirmed that ABCB1 confers resistance and identified 4 new genes that when knocked out lead to resistance to topoisomerase II inhibitors: C9orf82, SMARCB1, SMARCE1, and Keap1. All of these genes are related to repair of double stranded DNA breaks. For the most part, these deletions do not make cells resistant to topo I inhibitors.


*Given the major toxicities of doxorubicin and etoposide it would be useful to select patients whose tumors will be resistant to these agents. This panel identifies the genes that could help us make thischoice. We will now have to investigate these in animal and human studies.