Revisiting the IGF-1R as a breast cancer target

Abstract The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth fa...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Roudy Chiminch Ekyalongo, Douglas Yee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ff753cb1f1364c4681fe4a6c2ca7b956
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ff753cb1f1364c4681fe4a6c2ca7b956
record_format	dspace
spelling	oai:doaj.org-article:ff753cb1f1364c4681fe4a6c2ca7b9562021-12-02T16:05:45ZRevisiting the IGF-1R as a breast cancer target10.1038/s41698-017-0017-y2397-768Xhttps://doaj.org/article/ff753cb1f1364c4681fe4a6c2ca7b9562017-05-01T00:00:00Zhttps://doi.org/10.1038/s41698-017-0017-yhttps://doaj.org/toc/2397-768XAbstract The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation. Growth hormone elevation induces insulin resistance, hence a subsequent elevation of insulin and the potential for activation of insulin receptor. Second, the insulin-like growth factor-1 receptor and insulin receptor are highly homologous in amino acid sequence, structure, and function. These two receptors bind insulin, insulin-like growth factor-1 and insulin-like growth factor-2, to regulate glucose uptake and other cellular functions. Hybrid receptors composed of one chain of insulin-like growth factor-1 receptor and insulin receptor also participate in signaling. Third, since all the monoclonal antibodies were specific for insulin-like growth factor-1 receptor, any pathophysiologic role for insulin receptor was not inhibited. While the insulin-like growth factor-1 receptor tyrosine kinase inhibitors effectively inhibited both insulin-like growth factor-1 receptor and insulin receptor, these drugs are not being further developed likely due to their metabolic toxicities. Insulin-like growth factor-1/2 neutralizing antibodies are still being studied in early phase clinical trials. Perhaps a more comprehensive strategy of targeting the insulin-like growth factor-1 receptor network would be successful. For example, targeting receptor, ligand and downstream signaling molecules such as phosphatidylinositol 3′-kinase or particularly the insulin receptor substrate adapter proteins might result in a complete blockade of insulin-like growth factor-1 receptor/insulin receptor biological functions.Roudy Chiminch EkyalongoDouglas YeeNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 1, Iss 1, Pp 1-7 (2017)
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 Roudy Chiminch Ekyalongo Douglas Yee Revisiting the IGF-1R as a breast cancer target
description	Abstract The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation. Growth hormone elevation induces insulin resistance, hence a subsequent elevation of insulin and the potential for activation of insulin receptor. Second, the insulin-like growth factor-1 receptor and insulin receptor are highly homologous in amino acid sequence, structure, and function. These two receptors bind insulin, insulin-like growth factor-1 and insulin-like growth factor-2, to regulate glucose uptake and other cellular functions. Hybrid receptors composed of one chain of insulin-like growth factor-1 receptor and insulin receptor also participate in signaling. Third, since all the monoclonal antibodies were specific for insulin-like growth factor-1 receptor, any pathophysiologic role for insulin receptor was not inhibited. While the insulin-like growth factor-1 receptor tyrosine kinase inhibitors effectively inhibited both insulin-like growth factor-1 receptor and insulin receptor, these drugs are not being further developed likely due to their metabolic toxicities. Insulin-like growth factor-1/2 neutralizing antibodies are still being studied in early phase clinical trials. Perhaps a more comprehensive strategy of targeting the insulin-like growth factor-1 receptor network would be successful. For example, targeting receptor, ligand and downstream signaling molecules such as phosphatidylinositol 3′-kinase or particularly the insulin receptor substrate adapter proteins might result in a complete blockade of insulin-like growth factor-1 receptor/insulin receptor biological functions.
format	article
author	Roudy Chiminch Ekyalongo Douglas Yee
author_facet	Roudy Chiminch Ekyalongo Douglas Yee
author_sort	Roudy Chiminch Ekyalongo
title	Revisiting the IGF-1R as a breast cancer target
title_short	Revisiting the IGF-1R as a breast cancer target
title_full	Revisiting the IGF-1R as a breast cancer target
title_fullStr	Revisiting the IGF-1R as a breast cancer target
title_full_unstemmed	Revisiting the IGF-1R as a breast cancer target
title_sort	revisiting the igf-1r as a breast cancer target
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ff753cb1f1364c4681fe4a6c2ca7b956
work_keys_str_mv	AT roudychiminchekyalongo revisitingtheigf1rasabreastcancertarget AT douglasyee revisitingtheigf1rasabreastcancertarget
_version_	1718385187276980224

Revisiting the IGF-1R as a breast cancer target

Ejemplares similares