Research review paperHypoxic tumor microenvironment: Opportunities to develop targeted therapies

•Hypoxia is a constantly evolving participant in overall tumor growth and fate.•Changes due to hypoxic microenvironment can be exploited for designing targeted delivery systems.•Employing multiple targeting strategies can offer safer and more effective treatment outcomes.

In recent years, there has been great progress in the understanding of tumor biology and its surrounding microenvironment. Solid tumors create regions with low oxygen levels, generally termed as hypoxic regions. These hypoxic areas offer a tremendous opportunity to develop targeted therapies. Hypoxia is not a random by-product of the cellular milieu due to uncontrolled tumor growth; rather it is a constantly evolving participant in overall tumor growth and fate. This article reviews current trends and recent advances in drug therapies and delivery systems targeting hypoxia in the tumor microenvironment. In the first part, we give an account of important physicochemical changes and signaling pathways activated in the hypoxic microenvironment. This is then followed by various treatment strategies including hypoxia-sensitive signaling pathways and approaches to develop hypoxia-targeted drug delivery systems.