Emerging role of G9a in cancer stemness and promises as a therapeutic target

Abstract The histone methyltransferase G9a is well-documented for its implication in neoplastic growth. However, recent investigations have demonstrated a key involvement of this chromatin writer in maintaining the self-renewal and tumor-initiating capacities of cancer stem cells (CSCs). Direct inhi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Joshua R. Haebe, Christopher J. Bergin, Tamara Sandouka, Yannick D. Benoit
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b8971e79981c4eedbbfe56b1ef193610
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b8971e79981c4eedbbfe56b1ef193610
record_format	dspace
spelling	oai:doaj.org-article:b8971e79981c4eedbbfe56b1ef1936102021-11-14T12:16:43ZEmerging role of G9a in cancer stemness and promises as a therapeutic target10.1038/s41389-021-00370-72157-9024https://doaj.org/article/b8971e79981c4eedbbfe56b1ef1936102021-11-01T00:00:00Zhttps://doi.org/10.1038/s41389-021-00370-7https://doaj.org/toc/2157-9024Abstract The histone methyltransferase G9a is well-documented for its implication in neoplastic growth. However, recent investigations have demonstrated a key involvement of this chromatin writer in maintaining the self-renewal and tumor-initiating capacities of cancer stem cells (CSCs). Direct inhibition of G9a’s catalytic activity was reported as a promising therapeutic target in multiple preclinical studies. Yet, none of the available pharmacological inhibitors of G9a activity have shown success at the early stages of clinical testing. Here, we discuss central findings of oncogenic expression and activation of G9a in CSCs from different origins, as well as the impact of the suppression of G9a histone methyltransferase activity in such contexts. We will explore the challenges posed by direct and systemic inhibition of G9a activity in the perspective of clinical translation of documented small molecules. Finally, we will discuss recent advances in drug discovery as viable strategies to develop context-specific drugs, selectively targeting G9a in CSC populations.Joshua R. HaebeChristopher J. BerginTamara SandoukaYannick D. BenoitNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncogenesis, Vol 10, Iss 11, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Joshua R. Haebe Christopher J. Bergin Tamara Sandouka Yannick D. Benoit Emerging role of G9a in cancer stemness and promises as a therapeutic target
description	Abstract The histone methyltransferase G9a is well-documented for its implication in neoplastic growth. However, recent investigations have demonstrated a key involvement of this chromatin writer in maintaining the self-renewal and tumor-initiating capacities of cancer stem cells (CSCs). Direct inhibition of G9a’s catalytic activity was reported as a promising therapeutic target in multiple preclinical studies. Yet, none of the available pharmacological inhibitors of G9a activity have shown success at the early stages of clinical testing. Here, we discuss central findings of oncogenic expression and activation of G9a in CSCs from different origins, as well as the impact of the suppression of G9a histone methyltransferase activity in such contexts. We will explore the challenges posed by direct and systemic inhibition of G9a activity in the perspective of clinical translation of documented small molecules. Finally, we will discuss recent advances in drug discovery as viable strategies to develop context-specific drugs, selectively targeting G9a in CSC populations.
format	article
author	Joshua R. Haebe Christopher J. Bergin Tamara Sandouka Yannick D. Benoit
author_facet	Joshua R. Haebe Christopher J. Bergin Tamara Sandouka Yannick D. Benoit
author_sort	Joshua R. Haebe
title	Emerging role of G9a in cancer stemness and promises as a therapeutic target
title_short	Emerging role of G9a in cancer stemness and promises as a therapeutic target
title_full	Emerging role of G9a in cancer stemness and promises as a therapeutic target
title_fullStr	Emerging role of G9a in cancer stemness and promises as a therapeutic target
title_full_unstemmed	Emerging role of G9a in cancer stemness and promises as a therapeutic target
title_sort	emerging role of g9a in cancer stemness and promises as a therapeutic target
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/b8971e79981c4eedbbfe56b1ef193610
work_keys_str_mv	AT joshuarhaebe emergingroleofg9aincancerstemnessandpromisesasatherapeutictarget AT christopherjbergin emergingroleofg9aincancerstemnessandpromisesasatherapeutictarget AT tamarasandouka emergingroleofg9aincancerstemnessandpromisesasatherapeutictarget AT yannickdbenoit emergingroleofg9aincancerstemnessandpromisesasatherapeutictarget
_version_	1718429309779050496

Emerging role of G9a in cancer stemness and promises as a therapeutic target

Ejemplares similares