Suppression of tumor growth through disruption of hypoxia-inducible transcription

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