Trial watch: dexmedetomidine in cancer therapy

Dexmedetomidine (DEX) is a highly selective alpha 2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX has the capacity to alleviate inflammatory pain while limiting immunosuppressive glucocorticoid stress during major surgery, thus harboring therapeutic benefits for oncological procedures. Recently, the molecular mechanisms of DEX-mediated anticancer effects have been partially deciphered. Together with additional preclinical data, these mechanistic insights support the hypothesis that DEX-induced therapeutic benefits are mediated via the stimulation of adaptive anti-tumor immune responses. Similarly, published clinical trials including ancillary studies described an immunostimulatory role of DEX during the perioperative period of cancer surgery. The impact of DEX on long-term patient survival remains elusive. Nevertheless, DEX-mediated immunostimulation offers an interesting therapeutic option for onco-anesthesia. Our present review comprehensively summarizes data from preclinical and clinical studies as well as from ongoing trials with a distinct focus on the role of DEX in overcoming (tumor microenvironment (TME)-imposed) cancer therapy resistance. The objective of this update is to guide clinicians in their choice toward immunostimulatory onco-anesthetic agents that have the capacity to improve disease outcome.