Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK's structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies.

Pomella, S., Cassandri, M., Rita Braghini, M., Marampon, F., Alisi, A., R, R. (2022). New Insights on the Nuclear Functions and Targeting of FAK in Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(4), 1998 [10.3390/ijms23041998].

New Insights on the Nuclear Functions and Targeting of FAK in Cancer

Silvia Pomella;Matteo Cassandri;
2022-01-01

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK's structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies.
Pubblicato
Rilevanza internazionale
Recensione
Esperti anonimi
Settore MED/05
English
ATP-competitive inhibitors; FAK; PROTACs; adult cancers; allosteric inhibitors; combination therapy; pediatric cancers; targeted therapy
Pomella, S., Cassandri, M., Rita Braghini, M., Marampon, F., Alisi, A., R, R. (2022). New Insights on the Nuclear Functions and Targeting of FAK in Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(4), 1998 [10.3390/ijms23041998].
Pomella, S; Cassandri, M; Rita Braghini, M; Marampon, F; Alisi, A; R, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/311781
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