Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is the third leading cause of cancer-related mortality worldwide. Multifactorial drug resistance is regarded as the major cause of treatment failure in HCC. Accumulating evidence shows that the constituents of the...

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Main Authors: Jiaxin Zhang, Huiqiong Han, Lei Wang, Wenjia Wang, Mei Yang, Yanru Qin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.988956/full
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author Jiaxin Zhang
Huiqiong Han
Lei Wang
Wenjia Wang
Mei Yang
Yanru Qin
author_facet Jiaxin Zhang
Huiqiong Han
Lei Wang
Wenjia Wang
Mei Yang
Yanru Qin
author_sort Jiaxin Zhang
collection DOAJ
description Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is the third leading cause of cancer-related mortality worldwide. Multifactorial drug resistance is regarded as the major cause of treatment failure in HCC. Accumulating evidence shows that the constituents of the tumor microenvironment (TME), including cancer-associated fibroblasts, tumor vasculature, immune cells, physical factors, cytokines, and exosomes may explain the therapeutic resistance mechanisms in HCC. In recent years, anti-angiogenic drugs and immune checkpoint inhibitors have shown satisfactory results in HCC patients. However, due to enhanced communication between the tumor and TME, the effect of heterogeneity of the microenvironment on therapeutic resistance is particularly complicated, which suggests a more challenging research direction. In addition, it has been reported that the three-dimensional (3D) organoid model derived from patient biopsies is more intuitive to fully understand the role of the TME in acquired resistance. Therefore, in this review, we have focused not only on the mechanisms and targets of therapeutic resistance related to the contents of the TME in HCC but also provide a comprehensive description of 3D models and how they contribute to the exploration of HCC therapies.
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spelling doaj.art-94298e07d33346be95e1b6e9031927c32022-12-22T04:14:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.988956988956Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironmentJiaxin ZhangHuiqiong HanLei WangWenjia WangMei YangYanru QinHepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is the third leading cause of cancer-related mortality worldwide. Multifactorial drug resistance is regarded as the major cause of treatment failure in HCC. Accumulating evidence shows that the constituents of the tumor microenvironment (TME), including cancer-associated fibroblasts, tumor vasculature, immune cells, physical factors, cytokines, and exosomes may explain the therapeutic resistance mechanisms in HCC. In recent years, anti-angiogenic drugs and immune checkpoint inhibitors have shown satisfactory results in HCC patients. However, due to enhanced communication between the tumor and TME, the effect of heterogeneity of the microenvironment on therapeutic resistance is particularly complicated, which suggests a more challenging research direction. In addition, it has been reported that the three-dimensional (3D) organoid model derived from patient biopsies is more intuitive to fully understand the role of the TME in acquired resistance. Therefore, in this review, we have focused not only on the mechanisms and targets of therapeutic resistance related to the contents of the TME in HCC but also provide a comprehensive description of 3D models and how they contribute to the exploration of HCC therapies.https://www.frontiersin.org/articles/10.3389/fonc.2022.988956/fullhepatocellular carcinomatumor microenvironmenttherapeutic resistancetherapeutic targetsnovel drugspatient-derived organoids
spellingShingle Jiaxin Zhang
Huiqiong Han
Lei Wang
Wenjia Wang
Mei Yang
Yanru Qin
Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
Frontiers in Oncology
hepatocellular carcinoma
tumor microenvironment
therapeutic resistance
therapeutic targets
novel drugs
patient-derived organoids
title Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
title_full Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
title_fullStr Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
title_full_unstemmed Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
title_short Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
title_sort overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment
topic hepatocellular carcinoma
tumor microenvironment
therapeutic resistance
therapeutic targets
novel drugs
patient-derived organoids
url https://www.frontiersin.org/articles/10.3389/fonc.2022.988956/full
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