Hypoxia-inducible factors (HIFs), transcription factors that mediate the body’s response to low oxygen, are upregulated in many cancer types, which helps cancer cells grow in the oxygen-depleted environment of the tumour. Drugs inhibiting HIFs are attractive options for limiting cancer growth and are currently undergoing clinical trials in several cancer types. In this paper published in the Journal of Clinical Investigation, Gloria Cheng, Maria Prange-Barczynska, James Fielding and colleagues from Tammie Bishop’s and Peter Ratcliffe’s research groups investigate whether HIF-2 isoform inhibition has a side effect on the body’s normal responses to low oxygen, particularly the change in breathing rate. They found that doses of HIF-2 inhibitor similar to those reported to reduce cancer growth rapidly impaired the ventilatory response to low oxygen in mice. These were not off-target effects since disruption of the drug binding site on HIF-2 prevented this response to the drug. This study therefore suggests a need for caution when using HIF-2 inhibition to treat patients with a higher dependency on the ventilatory response to low oxygen, such as those with co-occurring respiratory disorders or those living at altitude.
Anti-cancer HIF-2 inhibition affects the hypoxic ventilatory response
31 January 2020
Researchers from Dr Tammie Bishop’s and Prof Sir Peter Ratcliffe’s laboratories show that an anti-cancer HIF inhibitor impairs the normal ventilatory response to low oxygen.