Cargando…

Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options

Aberrant bioactivity of the insulin-like growth factor (IGF) system results in the development and progression of several pathologic conditions including cancer. Preclinical studies have shown promising anti-cancer therapeutic potentials for anti-IGF targeted therapies. However, a clear but limited...

Descripción completa

Detalles Bibliográficos
Autores principales: Mancarella, Caterina, Morrione, Andrea, Scotlandi, Katia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392407/
https://www.ncbi.nlm.nih.gov/pubmed/34440844
http://dx.doi.org/10.3390/cells10082075
_version_ 1783743495906787328
author Mancarella, Caterina
Morrione, Andrea
Scotlandi, Katia
author_facet Mancarella, Caterina
Morrione, Andrea
Scotlandi, Katia
author_sort Mancarella, Caterina
collection PubMed
description Aberrant bioactivity of the insulin-like growth factor (IGF) system results in the development and progression of several pathologic conditions including cancer. Preclinical studies have shown promising anti-cancer therapeutic potentials for anti-IGF targeted therapies. However, a clear but limited clinical benefit was observed only in a minority of patients with sarcomas. The molecular complexity of the IGF system, which comprises multiple regulators and interactions with other cancer-related pathways, poses a major limitation in the use of anti-IGF agents and supports the need of combinatorial therapeutic strategies to better tackle this axis. In this review, we will initially highlight multiple mechanisms underlying IGF dysregulation in cancer and then focus on the impact of the IGF system and its complexity in sarcoma development and progression as well as response to anti-IGF therapies. We will also discuss the role of Ephrin receptors, Hippo pathway, BET proteins and CXCR4 signaling, as mediators of sarcoma malignancy and relevant interactors with the IGF system in tumor cells. A deeper understanding of these molecular interactions might provide the rationale for novel and more effective therapeutic combinations to treat sarcomas.
format Online
Article
Text
id pubmed-8392407
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83924072021-08-28 Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options Mancarella, Caterina Morrione, Andrea Scotlandi, Katia Cells Review Aberrant bioactivity of the insulin-like growth factor (IGF) system results in the development and progression of several pathologic conditions including cancer. Preclinical studies have shown promising anti-cancer therapeutic potentials for anti-IGF targeted therapies. However, a clear but limited clinical benefit was observed only in a minority of patients with sarcomas. The molecular complexity of the IGF system, which comprises multiple regulators and interactions with other cancer-related pathways, poses a major limitation in the use of anti-IGF agents and supports the need of combinatorial therapeutic strategies to better tackle this axis. In this review, we will initially highlight multiple mechanisms underlying IGF dysregulation in cancer and then focus on the impact of the IGF system and its complexity in sarcoma development and progression as well as response to anti-IGF therapies. We will also discuss the role of Ephrin receptors, Hippo pathway, BET proteins and CXCR4 signaling, as mediators of sarcoma malignancy and relevant interactors with the IGF system in tumor cells. A deeper understanding of these molecular interactions might provide the rationale for novel and more effective therapeutic combinations to treat sarcomas. MDPI 2021-08-13 /pmc/articles/PMC8392407/ /pubmed/34440844 http://dx.doi.org/10.3390/cells10082075 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mancarella, Caterina
Morrione, Andrea
Scotlandi, Katia
Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title_full Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title_fullStr Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title_full_unstemmed Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title_short Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
title_sort unraveling the igf system interactome in sarcomas exploits novel therapeutic options
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392407/
https://www.ncbi.nlm.nih.gov/pubmed/34440844
http://dx.doi.org/10.3390/cells10082075
work_keys_str_mv AT mancarellacaterina unravelingtheigfsysteminteractomeinsarcomasexploitsnoveltherapeuticoptions
AT morrioneandrea unravelingtheigfsysteminteractomeinsarcomasexploitsnoveltherapeuticoptions
AT scotlandikatia unravelingtheigfsysteminteractomeinsarcomasexploitsnoveltherapeuticoptions