Yashar Goorakani - Fasa student research committee, Fasa university of medical sciences, Fasa, Iran
Fatemeh Amoozegari - Fasa student research committee, Fasa university of medical sciences, Fasa, Iran
Mojtaba Farjami - Fasa Noncommunicable Diseases Research Center, Fasa university of medical sciences, Fasa, Iran- Pharmacology department, Fasa university of medical sciences, Fasa, Iran

The Hypoxic tumor microenvironment is the characteristic feature in the most solid tumors which is associated with resistance to chemotherapy and radiotherapy. The most of the solid tumors have regions with low oxygen tension which are associated with resistance to chemotherapy and worsen prognosis. Recent biological studies demonstrated that these regions are a favorable target for cancer treatment. There are some compounds which activate in hypoxic regions and leads to the generation of the free radicals which damage to DNA. The main purpose of the hypoxia-activated prodrugs (HAPs) or bioreductive prodrugs is to eradicate hypoxic regions. These prodrugs are different in potency and in different phases of clinical trials. The effectiveness of some agents has been confirmed in several clinical trials but it is still controversial. The aim of this review article is to discuss targeting tumor hypoxia as a pivotal target of cancer treatment, focusing on the mechanism of bioreductive prodrugs activation and current clinical progressions.