Inhibiting hypoxia-inducible factor 1 for cancer therapy

156Citations
Citations of this article
103Readers
Mendeley users who have this article in their library.

Abstract

Hypoxia has long been recognized as a common feature of solid tumors and a negative prognostic factor for response to treatment and survival of cancer patients. The discovery of hypoxia-inducible factor 1 (HIF-1), a molecular determinant of the response of mammalian cells to hypoxia, has led to the identification of a "molecular target" of hypoxia suitable for the development of cancer therapeutics. Early controversy about whether or not HIF-1 is a good target for therapy has not discouraged academic groups and pharmaceutical companies from actively engaging in the discovery of small-molecule inhibitors of HIF. However, what is the best strategy to inhibit HIF and how HIF inhibitors should be developed for treatment of human cancers is still poorly defined. In this review, aspects related to the identification and early development of novel HIF inhibitors are discussed. Identification and validation of pharmacodynamic end points relevant to the HIF-1 pathway is essential for a rational development of HIF inhibitors. Integration of these biomarkers in early clinical trials may provide valuable information to determine the contribution of HIF inhibitors to response to therapy. Finally, HIF inhibitors should be incorporated in combination strategies to effectively target multiple cellular components of the tumor microenvironment and redundant signaling pathways frequently deregulated in human cancer. Copyright © 2006 American Association for Cancer Research.

References Powered by Scopus

Targeting HIF-1 for cancer therapy

5812Citations
N/AReaders
Get full text

Hypoxia - A key regulatory factor in tumour growth

4654Citations
N/AReaders
Get full text

Role of HIF-1α in hypoxiamediated apoptosis, cell proliferation and tumour angiogenesis

2328Citations
N/AReaders
Get full text

Cited by Powered by Scopus

HIF-1 Inhibits Mitochondrial Biogenesis and Cellular Respiration in VHL-Deficient Renal Cell Carcinoma by Repression of C-MYC Activity

752Citations
N/AReaders
Get full text

The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by Tumor-Vascular Disrupting Agents

503Citations
N/AReaders
Get full text

Molecular biology of bone metastasis

369Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Melillo, G. (2006, September). Inhibiting hypoxia-inducible factor 1 for cancer therapy. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.MCR-06-0235

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 38

52%

Researcher 27

37%

Professor / Associate Prof. 7

10%

Lecturer / Post doc 1

1%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 41

50%

Medicine and Dentistry 23

28%

Biochemistry, Genetics and Molecular Bi... 12

15%

Chemistry 6

7%

Article Metrics

Tooltip
Mentions
References: 3

Save time finding and organizing research with Mendeley

Sign up for free