Trial watch: dexmedetomidine in cancer therapy

Abstract

Dexmedetomidine (DEX) is a highly selective α2-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.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia

“…A number of mostly in vitro studies in the last few years have shown that dexmedetomidine suppressed pro-inflammatory cytokines (IL-6, TNF-α, Necrosis factor) and antimicrobial effectors (ROS, RNS, NO, iNOS), as well as the local aggregation of neutrophils, leading to an in vitro anti-inflammatory effect that may be beneficial in critically ill patients in states with increased inflammatory response (SIRS) [102]. A number of pre-and mid-clinical studies suggest that dexmedetomidine may have anti-tumor effects by having indirect anti-inflammatory effects and directly inhibiting the survival, proliferation, and invasion of tumor cells [103].…”

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

“…The benefits of alpha-agonists such as clonidine and dexmedetomidine remain debated in surgery. Dexmedetomidine could exert both protumor or antitumor effects in vitro and in vivo through various mechanisms involving apoptotic and angiogenic signaling pathways as well as epigenetic changes [165]. Recent insights revealed that dexmedetomidine could decrease pro-inflammatory markers such as IL-6 and TNF-α, alleviate corticoid stress, and support the immune system by enhancing the CD8 + /CD4 + ratio and favoring the synthesis of the cytolytic IFN-γ in clinical trials [165].…”