sentence: The methods using GEAs to improve the selectivity of antitumor agents are known as gene ‐ directed ‐ enzyme prodrug therapy ( GDEPT ) and virus ‐ directed ‐ enzyme prodrug therapy ( VDEPT ) , and were also developed in the 1990s.68 Nitroreductases ( NTR ) are enzymes capable of reducing nitroaromatic groups into their corresponding anilines.69 Bacterial nitroreductases are well characterized and their activity is exploited for the activation of nitro ‐ substituted substrates70 , 71 , 72 , 73 by wild ‐ type NTR from Escherichia coli.74 Nitroreductase activity is also present in mammalian cells , but the enzymes responsible for the reduction of nitro groups have not been identified yet.75 Nevertheless , the increased nitroreductase activity of solid tumors is used for tumor ‐ specific fluorophore activation76 and activation of pro ‐ drugs in cancer therapy.77 Strict bioorthogonality is not ensured because NTR activity from endogenous enzymes is also observed in healthy mammalian cells , but employing bacterial or engineered NTRs can drastically increase the activation efficiency of nitroaromatic probes above the background of endogenous enzymes .