Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease

Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in c...

Descripción completa

Detalles Bibliográficos
Autores: Albiñana, Virginia, Gallardo Vara, Eunate, Rojas-P, Isabel de la, Recio-Poveda, Lucía, Aguado Sánchez, Tania, Canto-Cano, Ana, Aguirre, Daniel, Serra, Marcelo, González-Peramato, Pilar, Martínez-Piñeiro, Luis, Cuesta Martínez, Ángel, Botella, Luisa Maria
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/91712
Acceso en línea:https://hdl.handle.net/20.500.14352/91712
Access Level:acceso abierto
Palabra clave:577.175.8
615.361.45
616-006.04-02
β-adrenergic receptor antagonist
ICI-118,551
Propranolol
HIF
VHL
Anticarcinogenic
Bioquímica (Biología)
Oncología
2403 Bioquímica
3207.03 Carcinogénesis
3207.13 Oncología
Descripción
Sumario:Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.

Similares en LA Referencia