Importantly, however, because both TOP1-induced SSBs and TOP1 inhibition by CPT are rapidly reversible [38, 39], a transient inhibition of cell proliferation shortly before exposure to CPT is able to protect cancer cells from the drug’s cytotoxic effects [40, 41], especially when CPT is administered for a relatively short period of time and at lower concentrations, in a manner that mirrors the pharmacokinetics of SN-38 exposure in vivo [42, 43]. Here, TOP1 is linked to cancer.