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Review Open Access

Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review)

  • Authors:
    • Ting Yang
    • Jiao Tang
    • Muhammad Saqib Mudabbar
    • Huan Hu
    • Qiang Fu
    • Chunlan Pu
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan 610031, P.R. China, Department of Laboratory Medicine, Xindu District People's Hospital, Chengdu, Sichuan 610500, P.R. China, Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan 610031, P.R. China, Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan 610031, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 336
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    Published online on: October 5, 2026
       https://doi.org/10.3892/ijmm.2026.6007
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Abstract

Perioperative anesthesia is delivered during a brief but biologically dynamic interval in which surgical stress, inflammation, immune perturbation and tissue repair may alter the environment encountered by residual or disseminated tumor cells. Experimental studies indicate that anesthetic‑related agents can modify proliferation, apoptosis, epithelial‑mesenchymal transition, angiogenesis, immune surveillance and the tumor microenvironment. Translation to clinical benefit, however, has been inconsistent, in part because experimental models, routes and exposure schedules often differ substantially from perioperative pharmacology. Lidocaine and propofol illustrate this gap. In early breast cancer, a multicenter randomized trial reported improved 5‑year disease‑free and overall survival after preoperative peritumoral infiltration with 0.5% lidocaine, although independent confirmation is still required. By contrast, randomized comparisons of propofol‑based and volatile anesthesia, including long‑term follow‑up studies and GA‑CARES, have not demonstrated an overall‑ or disease‑free‑survival advantage for propofol. Mechanistic and perioperative biomarker studies remain informative, but these biomarkers are not validated surrogates for oncological outcomes. This review therefore evaluates anesthetic‑related interventions according to the exposure actually delivered, the level of mechanistic inference supported and the strength of clinical outcome evidence. Routine anesthetic choice should continue to follow established perioperative indications, whereas future cancer‑directed studies should align clinically achievable exposure with defined biological mechanisms, selected patient populations and clinically meaningful endpoints.
View Figures

Figure 1

Perioperative interface between
anesthetic-related interventions and cancer biology. Surgical
stress and related perioperative factors activate the HPA axis and
SNS and reshape the TME. Anesthetic-related agents may influence
tumor cells, immune cells, inflammatory and angiogenic mediators,
and tumor vasculature, with potential effects on proliferation,
EMT, invasion/metastasis, angiogenesis, inflammation, immune
evasion and apoptosis. These responses are context-dependent and
are not validated surrogates for cancer recurrence or survival.
EMT, epithelial-mesenchymal transition; HPA,
hypothalamic-pituitary-adrenal axis; ILs, interleukins; M1/M2,
macrophage polarization states; NK, natural killer; SNS,
sympathetic nervous system; TME, tumor microenvironment; TNF-α,
tumor necrosis factor-α; VEGF, vascular endothelial growth
factor.

Figure 2

Selected molecular pathways
associated with anesthetic-related agents in cancer models. The
schematic summarizes reported signaling and phenotypic responses to
lidocaine, propofol and volatile anesthetics, including VGSC-,
PI3K/AKT/mTOR-, Wnt/β-catenin-, AMPK-, NLRP3-, HIF-1α/VEGF- and
microRNA-associated pathways. Arrows indicate reported associations
rather than uniformly established direct drug-target interactions;
notably, the NLRP3 response reflects an immune-cell mechanism.
Effects vary with exposure and biological context. AKT, protein
kinase B; AMPK, AMP-activated protein kinase; EMT,
epithelial-mesenchymal transition; GABA(A), γ-aminobutyric acid
type A receptor; HIF-1α, hypoxia-inducible factor-1α; mTOR,
mechanistic target of rapamycin; NF-κB, nuclear factor-κB; NLRP3,
NLR family pyrin domain containing 3; PI3K, phosphoinositide
3-kinase; VEGF, vascular endothelial growth factor; VGSC,
voltage-gated sodium channel.

Figure 3

Context-dependent and host-mediated
responses to anesthetic-related drugs. Representative
context-dependent findings include lidocaine-associated EMT in A549
cells, propofol-associated Src/ZDHHC5-EZH2 signaling and stem-like
traits in glioma and HIF-1α-associated responses to volatile
anesthetics. Opioids and dexmedetomidine additionally modulate
immune, inflammatory, angiogenic and sympathetic pathways at the
host level. Downstream associations should not be interpreted as
direct molecular targets and the direction of response varies with
exposure, tumor and immune context. α2-AR, α2-adrenergic receptor;
DEX, dexmedetomidine; EMT, epithelial-mesenchymal transition; EZH2,
enhancer of zeste homolog 2; GABA(A), γ-aminobutyric acid type A
receptor; HIF-1α, hypoxia-inducible factor-1α; VGSC, voltage-gated
sodium channel; ZDHHC5, zinc finger DHHC-type palmitoyltransferase
5.

Figure 4

Translational framework for
anesthetic-related biological observations in clinical oncology.
The framework distinguishes routine anesthetic care, perioperative
pharmacological modulation and cancer-directed repurposing
according to agent, route, dose, duration, tissue exposure and
tumor-host context. Perioperative modulation relies on PK/PD
assessment and pharmacodynamic biomarkers, which are not validated
surrogates for recurrence or survival. Cancer-directed repurposing
additionally requires clinically achievable exposure, mechanistic
support, safety evaluation and randomized assessment using
clinically meaningful endpoints. DFS, disease-free survival; IV,
intravenous; OS, overall survival; PD, pharmacodynamic; PK,
pharmacokinetic; RCT, randomized controlled trial.
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Copy and paste a formatted citation
Spandidos Publications style
Yang T, Tang J, Mudabbar MS, Hu H, Fu Q and Pu C: Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review). Int J Mol Med 58: 336, 2026.
APA
Yang, T., Tang, J., Mudabbar, M.S., Hu, H., Fu, Q., & Pu, C. (2026). Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review). International Journal of Molecular Medicine, 58, 336. https://doi.org/10.3892/ijmm.2026.6007
MLA
Yang, T., Tang, J., Mudabbar, M. S., Hu, H., Fu, Q., Pu, C."Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review)". International Journal of Molecular Medicine 58.6 (2026): 336.
Chicago
Yang, T., Tang, J., Mudabbar, M. S., Hu, H., Fu, Q., Pu, C."Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review)". International Journal of Molecular Medicine 58, no. 6 (2026): 336. https://doi.org/10.3892/ijmm.2026.6007
Copy and paste a formatted citation
x
Spandidos Publications style
Yang T, Tang J, Mudabbar MS, Hu H, Fu Q and Pu C: Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review). Int J Mol Med 58: 336, 2026.
APA
Yang, T., Tang, J., Mudabbar, M.S., Hu, H., Fu, Q., & Pu, C. (2026). Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review). International Journal of Molecular Medicine, 58, 336. https://doi.org/10.3892/ijmm.2026.6007
MLA
Yang, T., Tang, J., Mudabbar, M. S., Hu, H., Fu, Q., Pu, C."Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review)". International Journal of Molecular Medicine 58.6 (2026): 336.
Chicago
Yang, T., Tang, J., Mudabbar, M. S., Hu, H., Fu, Q., Pu, C."Anesthetics and cancer biology: Translational evidence from perioperative modulation to drug repurposing (Review)". International Journal of Molecular Medicine 58, no. 6 (2026): 336. https://doi.org/10.3892/ijmm.2026.6007
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