Hypoxia-inducible factor-1: a possible link between inhalational anesthetics and tumor progression?

ABSTRACT

Cancer remains one of the major causes of death worldwide, and the global burden of the disease is rising continuously. Clinical retrospective data suggested that inhalational anesthetics might affect the prognosis of cancer patients, but the underlying molecular mechanism remained unknown. Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcription factor and mediates various cellular responses to hypoxia, including metabolism, cell death and survival, angiogenesis, oxygen delivery, immune evasion, and genomic adaptation. HIF-1 system has been shown to be the driving force of solid tumor progression and substantially contributes to the malignancy of cancer. Inhalational anesthetics such as isoflurane have been demonstrated to confer cytoprotection in a HIF-1-dependent manner in various vital organs. In addition, a recent study has demonstrated the pivotal involvement of HIF-1 in the impact of inhalational anesthetics on cancer cells. This review provides critical insights into the new understanding of cancer sensing of inhalational anesthetics and examines the recent understanding of the underlying molecular mechanisms. However, this area of research is just beginning and warrants further studies preclinically and clinically prior to making any conclusions that inhalational anesthetics may affect cancer outcomes. In addition, it is important to note that there is not enough evidence to support any change in the current clinical practice.