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      Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)

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          Abstract

          Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer. According to the American Cancer Society, among patients diagnosed with advanced liver cancer, HCC has the sixth-highest incident rate, resulting in a poor prognosis. Surgery, radiofrequency ablation, transcatheter arterial chemoembolization, radiation, chemotherapy, targeted therapy and immunotherapy are the current treatment options available. Immunotherapy, which has emerged as an innovative treatment strategy over the past decade, is serving a vital role in the treatment of advanced liver cancer. Since only a small number of individuals can benefit from immunotherapy, biomarkers are required to help clinicians identify the target populations for this precision medicine. These biomarkers, such as PD-1/PD-L1, tumor mutational burden and circulating tumor DNA, can be used to investigate interactions between immune checkpoint inhibitors and tumors. The present review summarizes information on the currently available biomarkers used for immunotherapy and the challenges that are present.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            The blockade of immune checkpoints in cancer immunotherapy.

            Drew M Pardoll (2012)
            Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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              Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

              Richard S Finn, Shukui Qin, Masafumi Ikeda … (2020)
              The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Exp Ther Med
                Journal ID (iso-abbrev): Exp Ther Med
                Journal ID (publisher-id): ETM
                Title: Experimental and Therapeutic Medicine
                Publisher: D.A. Spandidos
                ISSN (Print): 1792-0981
                ISSN (Electronic): 1792-1015
                Publication date Collection: December 2023
                Publication date (Electronic): 03 November 2023
                Publication date PMC-release: 03 November 2023
                Volume: 26
                Issue: 6
                Electronic Location Identifier: 586
                Affiliations
                Department of Medical Oncology, Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
                Author notes
                Correspondence to: Dr Ming Liu, Department of Medical Oncology, Gastric Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou, Chengdu, Sichuan 610041, P.R. China liuming629@ 123456wchscu.cn
                Article
                Publisher ID: ETM-26-6-12285
                DOI: 10.3892/etm.2023.12285
                PMC ID: 10665984
                SO-VID: ee0aea9b-c228-4e52-b80b-a11895fb5666
                Copyright © Copyright: © Cheng et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 22 March 2023
                Date accepted : 29 August 2023
                Funding
                Funding: This work was supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant no. ZYJC21043) and Sichuan Science and Technology Program (grant no. 23ZDYF2874).
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: hepatocellular carcinoma,immune checkpoint inhibitors,biomarkers,immunotherapy
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, biomarkers, immunotherapy

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