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Media type:
E-Article
Title:
Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease
Contributor:
Albiñana, Virginia;
Gallardo-Vara, Eunate;
de Rojas-P, Isabel;
Recio-Poveda, Lucia;
Aguado, Tania;
Canto-Cano, Ana;
Aguirre, Daniel T.;
Serra, Marcelo M.;
González-Peramato, Pilar;
Martínez-Piñeiro, Luis;
Cuesta, Angel M.;
Botella, Luisa Maria
Published:
MDPI AG, 2020
Published in:
Journal of Clinical Medicine, 9 (2020) 9, Seite 2740
Language:
English
DOI:
10.3390/jcm9092740
ISSN:
2077-0383
Origination:
Footnote:
Description:
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.