Cargando…

The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance

Breast cancer is the second leading cause of cancer-related death in women and is a complex disease with high intratumoral and intertumoral heterogeneity. Such heterogeneity is a major driving force behind failure of current therapies and development of resistance. Due to the limitations of conventi...

Descripción completa

Detalles Bibliográficos
Autores principales: Nandi, Ajeya, Chakrabarti, Rumela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608750/
https://www.ncbi.nlm.nih.gov/pubmed/33872192
http://dx.doi.org/10.1101/gad.342287.120
_version_ 1783604891996913664
author Nandi, Ajeya
Chakrabarti, Rumela
author_facet Nandi, Ajeya
Chakrabarti, Rumela
author_sort Nandi, Ajeya
collection PubMed
description Breast cancer is the second leading cause of cancer-related death in women and is a complex disease with high intratumoral and intertumoral heterogeneity. Such heterogeneity is a major driving force behind failure of current therapies and development of resistance. Due to the limitations of conventional therapies and inevitable emergence of acquired drug resistance (chemo and endocrine) as well as radio resistance, it is essential to design novel therapeutic strategies to improve the prognosis for breast cancer patients. Deregulated Notch signaling within the breast tumor and its tumor microenvironment (TME) is linked to poor clinical outcomes in treatment of resistant breast cancer. Notch receptors and ligands are also important for normal mammary development, suggesting the potential for conserved signaling pathways between normal mammary gland development and breast cancer. In this review, we focus on mechanisms by which Notch receptors and ligands contribute to normal mammary gland development and breast tumor progression. We also discuss how complex interactions between cancer cells and the TME may reduce treatment efficacy and ultimately lead to acquired drug or radio resistance. Potential combinatorial approaches aimed at disrupting Notch- and TME-mediated resistance that may aid in achieving in an improved patient prognosis are also highlighted.
format Online
Article
Text
id pubmed-7608750
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-76087502021-05-01 The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance Nandi, Ajeya Chakrabarti, Rumela Genes Dev Review Breast cancer is the second leading cause of cancer-related death in women and is a complex disease with high intratumoral and intertumoral heterogeneity. Such heterogeneity is a major driving force behind failure of current therapies and development of resistance. Due to the limitations of conventional therapies and inevitable emergence of acquired drug resistance (chemo and endocrine) as well as radio resistance, it is essential to design novel therapeutic strategies to improve the prognosis for breast cancer patients. Deregulated Notch signaling within the breast tumor and its tumor microenvironment (TME) is linked to poor clinical outcomes in treatment of resistant breast cancer. Notch receptors and ligands are also important for normal mammary development, suggesting the potential for conserved signaling pathways between normal mammary gland development and breast cancer. In this review, we focus on mechanisms by which Notch receptors and ligands contribute to normal mammary gland development and breast tumor progression. We also discuss how complex interactions between cancer cells and the TME may reduce treatment efficacy and ultimately lead to acquired drug or radio resistance. Potential combinatorial approaches aimed at disrupting Notch- and TME-mediated resistance that may aid in achieving in an improved patient prognosis are also highlighted. Cold Spring Harbor Laboratory Press 2020-11-01 /pmc/articles/PMC7608750/ /pubmed/33872192 http://dx.doi.org/10.1101/gad.342287.120 Text en © 2020 Nandi and Chakrabarti; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Review
Nandi, Ajeya
Chakrabarti, Rumela
The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title_full The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title_fullStr The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title_full_unstemmed The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title_short The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance
title_sort many facets of notch signaling in breast cancer: toward overcoming therapeutic resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608750/
https://www.ncbi.nlm.nih.gov/pubmed/33872192
http://dx.doi.org/10.1101/gad.342287.120
work_keys_str_mv AT nandiajeya themanyfacetsofnotchsignalinginbreastcancertowardovercomingtherapeuticresistance
AT chakrabartirumela themanyfacetsofnotchsignalinginbreastcancertowardovercomingtherapeuticresistance
AT nandiajeya manyfacetsofnotchsignalinginbreastcancertowardovercomingtherapeuticresistance
AT chakrabartirumela manyfacetsofnotchsignalinginbreastcancertowardovercomingtherapeuticresistance