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Annals of Surgical Oncology

28-09-2024 | Colorectal Cancer | Translational Research

Impact of Tumoral β2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer

Authors: Chika Komine, MD, Makoto Sohda, MD, PhD, Takehiko Yokobori, MD, PhD, Ikuma Shioi, MD, Naoya Ozawa, MD, PhD, Yuta Shibasaki, MD, PhD, Nobuhiro Nakazawa, MD, PhD, Katsuya Osone, MD, PhD, Takuya Shiraishi, MD, PhD, Takuhisa Okada, MD, PhD, Akihiko Sano, MD, PhD, Makoto Sakai, MD, PhD, Hiroomi Ogawa, MD, PhD, Kyoichi Kaira, MD, PhD, Ken Shirabe, MD, PhD, Hiroshi Saeki, MD, PhD

Published in: Annals of Surgical Oncology

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Abstract

Background

The β2-adrenergic receptor (β2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of β2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC.

Methods

β2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among β2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of β2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the β-blocker, propranolol, and other anticancer agents.

Results

High tumoral β2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model.

Conclusions

β2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing β-blockers could be beneficial for treating CRC resistant to existing treatment regimens.
Appendix
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Metadata
Title
Impact of Tumoral β2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer
Authors
Chika Komine, MD
Makoto Sohda, MD, PhD
Takehiko Yokobori, MD, PhD
Ikuma Shioi, MD
Naoya Ozawa, MD, PhD
Yuta Shibasaki, MD, PhD
Nobuhiro Nakazawa, MD, PhD
Katsuya Osone, MD, PhD
Takuya Shiraishi, MD, PhD
Takuhisa Okada, MD, PhD
Akihiko Sano, MD, PhD
Makoto Sakai, MD, PhD
Hiroomi Ogawa, MD, PhD
Kyoichi Kaira, MD, PhD
Ken Shirabe, MD, PhD
Hiroshi Saeki, MD, PhD
Publication date
28-09-2024
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-024-16195-8
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