Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. The aim of this study was to evaluate the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (Afatinib)-mediated signaling pathways, when used alone or in combination, on growth, cell cycle, cell death and autophagy, modulation of molecules involved in transduction pathways, in three human MM cell lines of different histotypes. The efficacy of the combined treatment was also evaluated in a murine epithelioid MM cell line both in vitro and in vivo. This study demonstrated that combined treatment with two inhibitors counteracting the activation of two different signaling pathways involved in neoplastic transformation and progression, such as those activated by ErbB and Hh signaling, is more effective than the single treatments in reducing MM growth in vitro and in vivo. This study may have clinical implications for the development of targeted therapy approaches for MM.

Bei, R., Benvenuto, M., Focaccetti, C., Fazi, S., Moretti, M., Nardozi, D., et al. (2022). Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo. JOURNAL OF TRANSLATIONAL MEDICINE, 20(1), 286 [10.1186/s12967-022-03490-9].

Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo

Bei R.
;
Focaccetti C.;Cifaldi L.;Palumbo C.;Bei R.;Barillari G.;Manzari V.;Modesti A.;
2022

Abstract

Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. The aim of this study was to evaluate the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (Afatinib)-mediated signaling pathways, when used alone or in combination, on growth, cell cycle, cell death and autophagy, modulation of molecules involved in transduction pathways, in three human MM cell lines of different histotypes. The efficacy of the combined treatment was also evaluated in a murine epithelioid MM cell line both in vitro and in vivo. This study demonstrated that combined treatment with two inhibitors counteracting the activation of two different signaling pathways involved in neoplastic transformation and progression, such as those activated by ErbB and Hh signaling, is more effective than the single treatments in reducing MM growth in vitro and in vivo. This study may have clinical implications for the development of targeted therapy approaches for MM.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/04
Settore MED/05
English
Con Impact Factor ISI
Afatinib
EGFR/ErbB receptors
GANT-61
Hedgehog/GLI pathway
Malignant mesothelioma
Animals
Cell Line, Tumor
Hedgehog Proteins
Humans
Mice
Signal Transduction
Zinc Finger Protein GLI1
ErbB Receptors
Mesothelioma, Malignant
Bei, R., Benvenuto, M., Focaccetti, C., Fazi, S., Moretti, M., Nardozi, D., et al. (2022). Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo. JOURNAL OF TRANSLATIONAL MEDICINE, 20(1), 286 [10.1186/s12967-022-03490-9].
Bei, R; Benvenuto, M; Focaccetti, C; Fazi, S; Moretti, M; Nardozi, D; Angiolini, V; Ciuffa, S; Cifaldi, L; Carrano, R; Palumbo, C; Miele, Mt; Bei, R; Barillari, G; Manzari, V; De Smaele, E; Modesti, A; Masuelli, L
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/303794
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