Impact of anesthetics on oncogenic signaling network: a review on propofol and isoflurane

Abstract

Propofol as an intravenous anesthetic and isoflurane as an inhalational/volatile anesthetic continue to be an important part of surgical anesthetic interventions worldwide. The impact of these anesthetics on tumor progression, immune modulation, and survival rates of cancer patients has been widely investigated. Although most of the preclinical studies have provided a beneficial effect of propofol over isoflurane or other volatile anesthetics, several investigations have shown contradictory results, which warrant more preclinical and clinical studies. Propofol mostly exhibits antitumor properties, whereas isoflurane being a cost‐effective anesthetic is frequently used. However, isoflurane has been also reported with protumorigenic activity. This review provides an overall perspective on the network of signaling pathways that may modulate several steps of tumor progression from inflammation, immunomodulation, epithelial–mesenchymal transition (EMT) to invasion, metastasis, angiogenesis, and cancer stemness and extracellular vesicles along with chemotherapeutic applications and clinical status of these anesthetics. A clear understanding of the mechanistic viewpoints of these anesthetics may pave the way for more prospective clinical trials with the ultimate goal of obtaining a safe and optimal anesthetic intervention that would prevent cancer recurrence and may influence better postoperative survival.

Dose‐dependent bidirectional pharmacological effects of vinorelbine‐based metronomic combination chemotherapy on tumor growth and metastasis and mechanisms in melanoma mouse model

“…Given the above, the present study elucidated a dose‐dependent bidirectional pharmacological action involving multiple mechanisms, including angiogenesis, apoptosis, and tumor immunity [53] (Figure 8). Notably, partial nonsignificant results in high‐dose combined regimens indicate the primary mechanism of metronomic combination chemotherapy seems to change with the doses or combinations of antineoplastic agents.…”

The potential anti-tumor effect of anesthetics on cancer by regulating autophagy

“…Reducing cancer cell proliferation and inducing their apoptosis are key strategies to prevent tumor growth. Recent studies have shown that anesthetics not only play a role in analgesia and sedation but can also inhibit drug resistance of tumor cells and inhibit tumor progression ( Ishikawa et al, 2021 ; Jing et al, 2022 ; Saha et al, 2022 ). To obtain a safe and effective anesthetic intervention, we need to understand the mechanism of these anesthetics to prevent cancer recurrence and promote longer postoperative survival.…”

Scaled up and telescoped synthesis of propofol under continuous-flow conditions

“…The mechanisms of action involve several neurotransmitter receptors, especially the GABA A receptor, and is considered a distinct sedative drug with low toxicity and rapid onset and metabolization [ 15 ]. In addition, evidence indicates that propofol can potentialize the antitumor effect of chemotherapy drugs, and studies of its application as a synergistic drug are under investigation [ 16 , 17 ]. Old uses and the recent needs justify the recognition of this drug as an essential medicine by the WHO since 2013 [ 18 ].…”