Drug Repositioning Based on the Reversal of Gene Expression Signatures Identifies TOP2A as a Therapeutic Target for Rectal Cancer.

ABSTRACT: Rectal cancer is a common disease with high mortality rates and limited therapeutic options. Here we combined the gene expression signatures of rectal cancer patients with the reverse drug-induced gene-expression profiles to identify drug repositioning candidates for cancer therapy. Among the predicted repurposable drugs, topoisomerase II inhibitors (doxorubicin, teniposide, idarubicin, mitoxantrone, and epirubicin) presented a high potential to reverse rectal cancer gene expression signatures. We showed that these drugs effectively reduced the growth of colorectal cancer cell lines closely representing rectal cancer signatures. We also found a clear correlation between topoisomerase 2A (TOP2A) gene copy number or expression levels with the sensitivity to topoisomerase II inhibitors

SUBMITTER: Carvalho RF 

PROVIDER: S-EPMC8583090 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature