Research Progress in the Study of Small Molecule Hypoxia-activated Prodrugs and HIF-1 Inhibitors Based on Hypoxia Microenvironment

Hypoxia is a prevalent feature of solid tumors and it is an important cause of tumor cell proliferation, metastasis, invasion, and development of resistance to radiotherapy. Therefore, tumor hypoxia is considered to be an important target for cancer diagnosis and treatment. Hypoxia-activated prodrugs can kill tumor cells by targeting tumor cells in hypoxic regions via electron reduction in a hypoxic microenvironment to produce and release cytotoxic metabolites. Currently, five major classes of hypoxia-activated prodrugs have been reported, including nitro compounds, quinones, nitrogen oxides, metal complexes, and azo compounds. The hypoxia-inducible factor-1(HIF-1) also plays an important role in the hypoxic survival and development of tumor cells, and inhibition of HIF-1 can inhibit its downstream gene-driven tumor angiogenesis, metastasis, drug resistance and other survival development processes. Currently, hypoxia-activated prodrugs with HIF-1 inhibitors are in clinical trials and have shown good anti-tumor activity and may play an important role in tumor diagnosis and treatment in the future.