February 3, 2020 –Research from Ludwig Oxford’s Tammie Bishop and Peter Ratcliffe shows that an anti-cancer HIF inhibitor impairs the normal ventilatory response to low oxygen.
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 tumor. 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, the researchers 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.