Hypoxia-Induced Tumor Progression and Drug Resistance: From Current Understandings to Future Perspectives

Hypoxia is a common feature of most cancers and contributes to aggressive phenotype and chemoresistance. Hypoxia inducible factor-1 (HIF-1) not only plays important roles in developmental and physiological hypoxic adaptation, but also a crucial mediator in hypoxiainduced tumor progression and chemoresistance. It has been demonstrated that HIF-1α is overexpressed in tumor cells by different kinds of mechanisms, including the presence of hypoxic stress, mutations in von Hippel Lindau (VHL), and hyperactivation of mitogen activated protein kinase and mammalian target of rapamycin signaling pathways. HIF-1 regulates anaerobic metabolism, drug efflux, and expression of anti-apoptotic genes, thus promoting tumor growth, survival, and drug resistance. Due to the common failure of classic chemotherapeutic agents in treating hypoxic cancers, some strategies have been developed to target tumors under hypoxic conditions including bioreductive drugs and inhibitors against pathways that were depended by tumor cells for their growth and survival. These new strategies may provide more effective and specific methods in targeting hypoxic tumors.

並列關鍵字

chemoresistance ； drug resistance ； hypoxia ； hypoxia-inducible factor ； tumor progression ； tumorigenesis

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