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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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 |
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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 |
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