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Cited by 71Cancer, Stress, Anesthesia, and Immune ResponseInflammatory mediators and NSAID effectsVagus Nerve Stimulation Research

Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β‐adrenergic and cyclooxygenase 2 signaling

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Ricon, Itay, Hanalis‐Miller, Tsipi, Haldar, Rita, Jacoby, Rebecca, Ben‐Eliyahu, Shamgar·2019·Cancer
DOI 10.1002/cncr.31594PMC PMC9385469
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Abstract

Evidence suggests that excess perioperative activation of the sympathetic nervous system and the consequent release of catecholamines (ie, epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate prometastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long‐term cancer outcomes nonproportionally to its short duration (days to weeks). Then, it analyzes the various mechanisms via which the excess release of catecholamines can facilitate the progression of cancer metastases in this context by directly affecting the malignant tissues and by regulating, via indirect pathways, immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically. In addition, this review addresses the need to supplement β‐adrenoreceptor blockade with cyclooxygenase 2 inhibition, especially during surgery and shortly thereafter, because similar mechanisms are simultaneously activated by surgery‐induced inflammatory responses. Importantly, this review presents translational and clinical evidence showing that perioperative β‐adrenoreceptor blockade and cyclooxygenase 2 inhibition can reduce the prometastatic process and cancer recurrence, and the clinical feasibility and safety of this approach are demonstrated as well. Lastly, alternative psychophysiological approaches to the use of β‐adrenergic blockers are presented because a substantial portion of patients have medical contraindications to this pharmacological treatment. The adaptation of existing psychophysiological interventions to the perioperative period and principles for constructing new approaches are discussed and exemplified. Overall, pharmacobehavioral interventions, separately or in combination, could transform the perioperative timeframe from being a prominent facilitator of metastatic progression to an opportunity for arresting or eliminating residual disease, potentially improving long‐term survival rates in cancer patients.

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  • A combined treatment with betablockers and COX-inhibitors in terms of drug repurposing promises an easy and effective approach to mitigate these effects.

    “A combined treatment with betablockers and cyclooxygenase inhibitors (COX-inhibitors) in terms of drug repurposing promises an easy and effective approach to mitigate these effects [8].”

    From Pancreatic resection with perioperative drug repurposing of propranolol and etodolac – the phase II randomized controlled PROSPER trial (2025) · cites this paper as [8]

    The section on perioperative clinical studies reports that combined propranolol and etodolac improved biological markers and may reduce metastatic effects. It also says the clinical trials were small, the colorectal cancer disease-free survival improvement was not statistically significant, and safety precautions are needed. Thus the paper supports the approach as promising, but not as an established easy and effective way to mitigate those effects. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ricon, I., Hanalis‐Miller, T., Haldar, R., Jacoby, R., & Ben‐Eliyahu, S.
Affiliations
  • Psychoneuroimmunology Laboratory, School of Psychological Sciences Tel Aviv University Tel Aviv Israel
  • Tel Aviv University (IL)
  • Academic College of Tel Aviv-Yafo (IL)
Corresponding author
Ben‐Eliyahu, Shamgar
ORCID
Venue
Cancer
Publisher
Wiley
Published
2018-10-06
Volume
125
Issue
1
Pages
45-56
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.31594
PMC
PMC9385469
OpenAlex
W2894574865
Cited by
71
References
11
Citations by year
2026: 7 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 15 · 2021: 10 · 2020: 12 · 2019: 5 · 2018: 1
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (P01 CA163233)
  • National Institutes of Health (CA125456, CA172138)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
perioperative care, tumor recurrence, beta-adrenergic blockade, COX-2 inhibition, catecholamines, sympathetic activation, metastasis, tumor microenvironment, epinephrine, norepinephrine
MeSH terms
Adrenergic beta-Antagonists, Catecholamines, Drug Synergism, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Signal Transduction, Randomized Controlled Trials as Topic, Cyclooxygenase 2 Inhibitors, Precision Medicine, Perioperative Period

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