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.

Perrone, C., Pomella, S., Cassandri, M., Rita Braghini, M., Pezzella, M., Locatelli, F., et al. (2020). FAK Signaling in Rhabdomyosarcoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(22), 1-19 [10.3390/ijms21228422].

FAK Signaling in Rhabdomyosarcoma

Silvia Pomella;Matteo Cassandri;
2020-01-01

Abstract

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.
2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/05 - PATOLOGIA CLINICA
English
rhabdomyosarcoma; FAK; focal adhesion complex; sarcoma; FAK inhibitors; cell migration; cell invasion; kinase; myogenesis
Perrone, C., Pomella, S., Cassandri, M., Rita Braghini, M., Pezzella, M., Locatelli, F., et al. (2020). FAK Signaling in Rhabdomyosarcoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(22), 1-19 [10.3390/ijms21228422].
Perrone, C; Pomella, S; Cassandri, M; Rita Braghini, M; Pezzella, M; Locatelli, F; Rota, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/311790
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