Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 34, Issue 18, Pages 1484-1497Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2019.7935
Keywords
targeted molecular therapy; HIF-1; metastasis; cancer therapy
Funding
- Natural Science Foundation of Hubei Province [2019CFB591]
- Central Funds Guiding the Local Science and Technology Development of Hubei Province [2019ZYYD066]
- Singapore Ministry of Health's National Medical Research Council
- National Research Foundation Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiatives
- NUHS Seed Grant
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Hypoxia plays a crucial role in the tumor microenvironment, correlating with tumor metastasis and prognosis. HIF-1α, a key molecule, is involved in multiple crucial steps in the metastatic cascade. Currently, researchers are focusing on potential pharmacological interventions and developing HIF-1 inhibitors to block tumor metastasis.
Significance: Hypoxia is emerging as a crucial regulator of the tumor microenvironment; it governs the metastatic potential of multiple primary cancers. It is also potentially involved in the regulation of tumorigenesis, tumor metabolism, and proangiogenic activity. Recent Advances: A wealth of clinical data across a wide range of cancer types has revealed strong correlations between hypoxia or the overexpression of hypoxia-inducible transcription factors and the rates of distant metastases and poor prognoses. Hypoxia-inducible factor (HIF)-1 alpha, one of the key regulatory molecules of the HIF-1 signaling pathways, is involved in multiple crucial steps in the metastatic cascade. Critical Issues: Here, we present recent findings on the roles of the HIF-1 complex in tumor metastasis and highlight the potential of HIF-1 alpha as a target for abrogating tumor metastasis. Moreover, we systematically describe the regulatory role of HIF-1 at each step of the metastatic cascade. Finally, we present the most recent advances in potential pharmacological interventions and the development of specific HIF-1 inhibitors for blocking tumor metastasis. Future Directions: Well-designed clinical trials are urgently needed to validate the anti-metastatic activity of HIF-1 inhibitors discovered in preclinical models.
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