The replicative cmg helicase: The ideal target for cancer therapy

Abstract

This review focuses on Cdc45-Mcm2-7-GINS (CMG) helicase which is a key component of the cellular replication machinery and a new promising target for cancer therapy. In normal cells, only a small propor-tion of helicases becomes activated through the step-wise acquisition of all necessary subunits during genome replication and a large quantity of reserve dormant helicases exist to replace inhibited helicases, making the normal cells insensitive to helicase inhibition. The collective evidence in the field shows that in contrast to normal cells, cancer cells have a significantly reduced pool of dormant helicases and might be vulnerable to CMG helicase inhibitors. Functional studies confirm that targeted inhibition of CMG helicase could be a strong and specific anticancer approach that ensures efficiency against a broad spectrum of cancers and limited adverse effects on normal cells. We anticipate that therapeutics that inhibit CMG helicase can be used not only as a stand-alone therapy but also as effective chemosensitizers in combination with other drugs, thus increasing their clinical application.