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FAK Signaling in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite...

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Autores principales: Perrone, Clara, Pomella, Silvia, Cassandri, Matteo, Braghini, Maria Rita, Pezzella, Michele, Locatelli, Franco, Rota, Rossella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697003/
https://www.ncbi.nlm.nih.gov/pubmed/33182556
http://dx.doi.org/10.3390/ijms21228422
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author Perrone, Clara
Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Pezzella, Michele
Locatelli, Franco
Rota, Rossella
author_facet Perrone, Clara
Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Pezzella, Michele
Locatelli, Franco
Rota, Rossella
author_sort Perrone, Clara
collection PubMed
description Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors’ activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors. In this review, we summarize the data on FAK expression and modulation in RMS. Moreover, we give an overview of the approaches to inhibit FAK in both preclinical and clinical cancer settings.
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spelling pubmed-76970032020-11-29 FAK Signaling in Rhabdomyosarcoma Perrone, Clara Pomella, Silvia Cassandri, Matteo Braghini, Maria Rita Pezzella, Michele Locatelli, Franco Rota, Rossella Int J Mol Sci Review Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors’ activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors. In this review, we summarize the data on FAK expression and modulation in RMS. Moreover, we give an overview of the approaches to inhibit FAK in both preclinical and clinical cancer settings. MDPI 2020-11-10 /pmc/articles/PMC7697003/ /pubmed/33182556 http://dx.doi.org/10.3390/ijms21228422 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Perrone, Clara
Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Pezzella, Michele
Locatelli, Franco
Rota, Rossella
FAK Signaling in Rhabdomyosarcoma
title FAK Signaling in Rhabdomyosarcoma
title_full FAK Signaling in Rhabdomyosarcoma
title_fullStr FAK Signaling in Rhabdomyosarcoma
title_full_unstemmed FAK Signaling in Rhabdomyosarcoma
title_short FAK Signaling in Rhabdomyosarcoma
title_sort fak signaling in rhabdomyosarcoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697003/
https://www.ncbi.nlm.nih.gov/pubmed/33182556
http://dx.doi.org/10.3390/ijms21228422
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