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Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches

The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1...

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Autores principales: Xulu, Kutlwano Rekgopetswe, Nweke, Ekene Emmanuel, Augustine, Tanya Nadine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469897/
https://www.ncbi.nlm.nih.gov/pubmed/37662839
http://dx.doi.org/10.3389/fgene.2023.1087432
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author Xulu, Kutlwano Rekgopetswe
Nweke, Ekene Emmanuel
Augustine, Tanya Nadine
author_facet Xulu, Kutlwano Rekgopetswe
Nweke, Ekene Emmanuel
Augustine, Tanya Nadine
author_sort Xulu, Kutlwano Rekgopetswe
collection PubMed
description The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1 and BRCA2, and hormone receptors. However, even within each subtype, heterogeneity that is driven by underlying evolutionary mechanisms is suggested to underlie poor response to therapy, variance in disease progression, recurrence, and relapse. Intratumoral heterogeneity highlights that the evolvability of tumor cells depends on interactions with cells of the tumor microenvironment. The complexity of the tumor microenvironment is being unraveled by recent advances in screening technologies such as high throughput sequencing; however, there remain challenges that impede the practical use of these approaches, considering the underlying biology of the tumor microenvironment and the impact of selective pressures on the evolvability of tumor cells. In this review, we will highlight the advances made thus far in defining the molecular heterogeneity in breast cancer and the implications thereof in diagnosis, the design and application of targeted therapies for improved clinical outcomes. We describe the different precision-based approaches to diagnosis and treatment and their prospects. We further propose that effective cancer diagnosis and treatment are dependent on unpacking the tumor microenvironment and its role in driving intratumoral heterogeneity. Underwriting such heterogeneity are Darwinian concepts of natural selection that we suggest need to be taken into account to ensure evolutionarily informed therapeutic decisions.
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spelling pubmed-104698972023-09-01 Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches Xulu, Kutlwano Rekgopetswe Nweke, Ekene Emmanuel Augustine, Tanya Nadine Front Genet Genetics The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1 and BRCA2, and hormone receptors. However, even within each subtype, heterogeneity that is driven by underlying evolutionary mechanisms is suggested to underlie poor response to therapy, variance in disease progression, recurrence, and relapse. Intratumoral heterogeneity highlights that the evolvability of tumor cells depends on interactions with cells of the tumor microenvironment. The complexity of the tumor microenvironment is being unraveled by recent advances in screening technologies such as high throughput sequencing; however, there remain challenges that impede the practical use of these approaches, considering the underlying biology of the tumor microenvironment and the impact of selective pressures on the evolvability of tumor cells. In this review, we will highlight the advances made thus far in defining the molecular heterogeneity in breast cancer and the implications thereof in diagnosis, the design and application of targeted therapies for improved clinical outcomes. We describe the different precision-based approaches to diagnosis and treatment and their prospects. We further propose that effective cancer diagnosis and treatment are dependent on unpacking the tumor microenvironment and its role in driving intratumoral heterogeneity. Underwriting such heterogeneity are Darwinian concepts of natural selection that we suggest need to be taken into account to ensure evolutionarily informed therapeutic decisions. Frontiers Media S.A. 2023-08-17 /pmc/articles/PMC10469897/ /pubmed/37662839 http://dx.doi.org/10.3389/fgene.2023.1087432 Text en Copyright © 2023 Xulu, Nweke and Augustine. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Xulu, Kutlwano Rekgopetswe
Nweke, Ekene Emmanuel
Augustine, Tanya Nadine
Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title_full Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title_fullStr Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title_full_unstemmed Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title_short Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
title_sort delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469897/
https://www.ncbi.nlm.nih.gov/pubmed/37662839
http://dx.doi.org/10.3389/fgene.2023.1087432
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