TOP1 and cancer: Although CPTs are presently the only Top1 inhibitors clinically approved for cancer therapy, they have intrinsic drawbacks such as: 1) CPTs are chemically unstable and rapidly convert to a carboxylate form that binds to plasma proteins; 2) the Top1-DNA-drug cleavage complex reverses within minutes after drug removal, requiring long infusion time of the drug; 3) CPTs are rapidly and extensively transported outside of the cell by cellular efflux pumps; 4) the side-effects of CPTs are dose-limiting and potentially severe [17].