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Kwee et al. Hepatoma Res 2021;7:8 Hepatoma Research
DOI: 10.20517/2394-5079.2020.124

Review Open Access

Beta-catenin activation and immunotherapy
resistance in hepatocellular carcinoma: mechanisms

and biomarkers

Sandi A. Kwee , Maarit Tiirikainen 1
1,2
1 Cancer Biology Program (SAK) and Population Sciences in the Pacific Program (MT), University of Hawaii Cancer Center,
University of Hawaii, Honolulu, Hawaii 96813, USA.
2 Hamamatsu/Queen’s PET Imaging Center, The Queen’s Medical Center, Honolulu, Hawaii 96813, USA.

Correspondence to: Dr. Sandi A. Kwee, Hamamatsu/Queen’s PET Imaging Center, The Queen’s Medical Center, 1301 Punchbowl
St. Honolulu, Hawaii 96813, USA. E-mail: kwee@hawaii.edu

How to cite this article: Kwee SA, Tiirikainen M. Beta-catenin activation and immunotherapy resistance in hepatocellular
carcinoma: mechanisms and biomarkers. Hepatoma Res 2021;7:8. http://dx.doi.org/10.20517/2394-5079.2020.124

Received: 14 Oct 2020 First Decision: 27 Oct 2020 Revised: 27 Oct 2020 Accepted: 28 Oct 2020 Published: 7 Jan 2020

Academic Editor: David M. Lubman Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Received: First Decision: Revised: Accepted: Published:
Abstract
Science Editor: Copy Editor: Production Editor: Jing Yu Mutations involving CTNNB1, the gene encoding beta-catenin, and other molecular alterations that affect the
Wnt/beta-catenin signaling pathway are exceptionally common in hepatocellular carcinoma. Several of these
alterations have also been associated with scarcity of immune cells in the tumor microenvironment and poor
clinical response to immune checkpoint inhibitor therapy. In light of these associations, tumor biomarkers of beta-
catenin status could have the potential to serve as clinical predictors of immunotherapy outcome. This editorial
review article summarizes recent pre-clinical and clinical research pertaining to associations between beta-catenin
activation and diminished anti-tumor immunity. Potential non-invasive biomarkers that may provide a window into
this oncogenic mechanism of immune evasion are also presented and discussed.

Keywords: Hepatocellular carcinoma, immunotherapy, immune checkpoint, biomarkers, positron emission
tomography, beta-catenin

BACKGROUND
Hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced clinical stage or precluded from
[1,2]
surgery by poor underlying liver function . Patients with clinically-advanced HCC have poor survival,

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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