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The perplexity of targeting genetic alterations in hepatocellular carcinoma
Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effec...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376083/ https://www.ncbi.nlm.nih.gov/pubmed/32699957 http://dx.doi.org/10.1007/s12032-020-01392-8 |
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author | Barone, Michele Di Leo, Alfredo Sabbà, Carlo Mazzocca, Antonio |
author_facet | Barone, Michele Di Leo, Alfredo Sabbà, Carlo Mazzocca, Antonio |
author_sort | Barone, Michele |
collection | PubMed |
description | Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effective therapeutic strategy preventing HCC. However, the failure of most targeted therapies has raised much perplexity regarding the role of genetic alterations in driving cancer as the main paradigm. Here, we discuss the methodological and conceptual limitations of targeting genetic alterations and their products that may explain the limited success of the novel mechanism-based drugs in the treatment of HCC. In light of these limitations and despite the era of the so-called “precision medicine,” prevention and early diagnosis of conditions predisposing to HCC remain the gold standard approach to prevent the development of this type of cancer. Finally, a paradigm shift to a more systemic approach to cancer is required to find optimal therapeutic solutions to treat this disease. |
format | Online Article Text |
id | pubmed-7376083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-73760832020-07-27 The perplexity of targeting genetic alterations in hepatocellular carcinoma Barone, Michele Di Leo, Alfredo Sabbà, Carlo Mazzocca, Antonio Med Oncol Perspectives in Oncology Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effective therapeutic strategy preventing HCC. However, the failure of most targeted therapies has raised much perplexity regarding the role of genetic alterations in driving cancer as the main paradigm. Here, we discuss the methodological and conceptual limitations of targeting genetic alterations and their products that may explain the limited success of the novel mechanism-based drugs in the treatment of HCC. In light of these limitations and despite the era of the so-called “precision medicine,” prevention and early diagnosis of conditions predisposing to HCC remain the gold standard approach to prevent the development of this type of cancer. Finally, a paradigm shift to a more systemic approach to cancer is required to find optimal therapeutic solutions to treat this disease. Springer US 2020-07-22 2020 /pmc/articles/PMC7376083/ /pubmed/32699957 http://dx.doi.org/10.1007/s12032-020-01392-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Perspectives in Oncology Barone, Michele Di Leo, Alfredo Sabbà, Carlo Mazzocca, Antonio The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title | The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title_full | The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title_fullStr | The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title_full_unstemmed | The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title_short | The perplexity of targeting genetic alterations in hepatocellular carcinoma |
title_sort | perplexity of targeting genetic alterations in hepatocellular carcinoma |
topic | Perspectives in Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376083/ https://www.ncbi.nlm.nih.gov/pubmed/32699957 http://dx.doi.org/10.1007/s12032-020-01392-8 |
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