Suppression of tumor growth through disruption of hypoxia-inducible transcription

Abstract

Chronic hypoxia, a hallmark of many tumors, is associated with angiogenesis and tumor progression. Strategies to treat tumors have been developed in which tumor cells are targeted with drugs or gene-therapy vectors specifically activated under hypoxic conditions. Here we report a different approach, in which the normal transcriptional response to hypoxia is selectively disrupted. Our data indicate that specific blockade of the interaction of hypoxia-inducible factor with the CH1 domain of its p300 and CREB binding protein transcriptional coactivators leads to attenuation of hypoxia-inducible gene expression and diminution of tumor growth. Thus, disrupting the normal co-activational response to hypoxia may be a new and useful therapeutic strategy.

Cite this article

Kung, A., Wang, S., Klco, J. et al. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 6, 1335–1340 (2000). https://doi.org/10.1038/82146

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