Published in:
01-12-2018 | Cancer Anesthesia (B Riedel and V Gottumukkala, Section
Editors)
Perioperative Stress, Inflammation, and Cancer Progression:
Opportunities for Intervention in Breast and Colorectal Cancer Surgery Utilizing
Beta-Adrenergic Blockade and COX-2 Inhibition
Authors:
Avital Fischer, Shamgar Ben-Eliyahu
Published in:
Current Anesthesiology Reports
|
Issue 4/2018
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Abstract
Purpose of review
This review explores the blockade of cyclooxygenase
(COX)-2/prostaglandin and catecholamine/beta(β)-adrenergic signaling as
opportunities to enhance the curative potential of surgical excision of breast
and colorectal cancer malignancies.
Recent findings
Phase-II randomized placebo-controlled biomarker clinical trials,
employing perioperative administration of the COX-2 inhibitor etodolac and the
β-adrenergic antagonist propranolol, have shown improved biomarkers associated
with both breast and colorectal cancer progression. Tumor
epithelial-to-mesenchymal transition (EMT) status and tumor transcription
activity levels of GATA-1, GATA-2, EGR3, and STAT-3 were reduced, while
anti-cancer immune parameters within the tumor microenvironment improved
perioperatively. Increased tumor-associated B cells and NK cells and reduced
tumor-associated monocytes were noted. Reduced systemic pro-inflammatory markers
IL-6 and CRP were indicated, starting before surgery.
Summary
Improved biomarkers of tumor-associated (i) anti-metastatic
transcriptional activity, (ii) anti-metastatic immune function, and (iii)
reduced systemic inflammatory indices were observed following the combined
administration of etodolac and propranolol. These findings support future
investigation with larger clinical trials to test long-term cancer
outcomes.