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Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact

SIMPLE SUMMARY: Resistance to antiangiogenic therapy represents a challenge in the therapeutic approach for hepatocellular carcinoma (HCC). The advent of immune checkpoint inhibitors (ICIs) seems to be a solution to this issue; however, other gaps have emerged since they have only been shown to prov...

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Autores principales: Federico, Piera, Giunta, Emilio Francesco, Tufo, Andrea, Tovoli, Francesco, Petrillo, Angelica, Daniele, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776845/
https://www.ncbi.nlm.nih.gov/pubmed/36551730
http://dx.doi.org/10.3390/cancers14246245
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author Federico, Piera
Giunta, Emilio Francesco
Tufo, Andrea
Tovoli, Francesco
Petrillo, Angelica
Daniele, Bruno
author_facet Federico, Piera
Giunta, Emilio Francesco
Tufo, Andrea
Tovoli, Francesco
Petrillo, Angelica
Daniele, Bruno
author_sort Federico, Piera
collection PubMed
description SIMPLE SUMMARY: Resistance to antiangiogenic therapy represents a challenge in the therapeutic approach for hepatocellular carcinoma (HCC). The advent of immune checkpoint inhibitors (ICIs) seems to be a solution to this issue; however, other gaps have emerged since they have only been shown to provide benefit in approximately 20% of patients. Combination strategies have introduced in clinical development to overcome this issue. This review deals with the resistance to antiangiogenic drugs by focusing on two protagonists, the tumor microenvironment and vascular normalization, to offer possible overcoming strategies. ABSTRACT: Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new opportunity; however, their use has highlighted other issues: the vascular normalization compared to a vessel pruning to promote the delivery of an active cancer immunotherapy and the development of resistance to immunotherapy which leads to a better selection of patients as candidates for ICIs. Nevertheless, the combination of antiangiogenic therapy plus ICIs represents an intriguing approach with high potential to improve the survival of these patients. Waiting for results from ongoing clinical trials, this review depicts the current knowledge about the resistance to antiangiogenic drugs in HCC. It could also provide updated information to clinicians focusing on the most effective combinations or sequential approaches in this regard, based on molecular mechanisms.
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spelling pubmed-97768452022-12-23 Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact Federico, Piera Giunta, Emilio Francesco Tufo, Andrea Tovoli, Francesco Petrillo, Angelica Daniele, Bruno Cancers (Basel) Review SIMPLE SUMMARY: Resistance to antiangiogenic therapy represents a challenge in the therapeutic approach for hepatocellular carcinoma (HCC). The advent of immune checkpoint inhibitors (ICIs) seems to be a solution to this issue; however, other gaps have emerged since they have only been shown to provide benefit in approximately 20% of patients. Combination strategies have introduced in clinical development to overcome this issue. This review deals with the resistance to antiangiogenic drugs by focusing on two protagonists, the tumor microenvironment and vascular normalization, to offer possible overcoming strategies. ABSTRACT: Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new opportunity; however, their use has highlighted other issues: the vascular normalization compared to a vessel pruning to promote the delivery of an active cancer immunotherapy and the development of resistance to immunotherapy which leads to a better selection of patients as candidates for ICIs. Nevertheless, the combination of antiangiogenic therapy plus ICIs represents an intriguing approach with high potential to improve the survival of these patients. Waiting for results from ongoing clinical trials, this review depicts the current knowledge about the resistance to antiangiogenic drugs in HCC. It could also provide updated information to clinicians focusing on the most effective combinations or sequential approaches in this regard, based on molecular mechanisms. MDPI 2022-12-18 /pmc/articles/PMC9776845/ /pubmed/36551730 http://dx.doi.org/10.3390/cancers14246245 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Federico, Piera
Giunta, Emilio Francesco
Tufo, Andrea
Tovoli, Francesco
Petrillo, Angelica
Daniele, Bruno
Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title_full Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title_fullStr Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title_full_unstemmed Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title_short Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact
title_sort resistance to antiangiogenic therapy in hepatocellular carcinoma: from molecular mechanisms to clinical impact
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776845/
https://www.ncbi.nlm.nih.gov/pubmed/36551730
http://dx.doi.org/10.3390/cancers14246245
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