Bioreductive antineoplasic agents: advances and challenges after 20 years

Solid tumors are frequently affected by the presence of hypoxic cells, originating anomalous and disordered cell growth. This subpopulation presents resistance to conventional chemotherapy agents and radiotherapy, due to the difficulties of reaching the target region, the permanence in the G0 phase of cell cycle and the low local concentration of oxygen. The use of hypoxia activated prodrugs becomes, in this scenario, an effective and selective alternative in cancer therapy, though not yet available for clinical use in solid tumor treatment. Twenty years after the publication of the paper intitled "Agentes Antineoplasicos Biorredutiveis: Uma Nova Alternativa para o Tratamento de Tumores Solidos" in the Quimica Nova journal (2002), the current essay aims to identify the advances in the pre-clinical and clinical studies regarding the development of new hypoxia-directed drugs and the improvement of the molecules previously studied. Moreover, to clarify the main challenges for the implementation and success of this drug class, in order to identify the hindrances for the preparation of a bioavailable, safe and selective drug.