Albiñana, VirginiaGallardo Vara, EunateRojas-P, Isabel de laRecio-Poveda, LucíaAguado Sánchez, TaniaCanto-Cano, AnaAguirre, DanielSerra, MarceloGonzález-Peramato, PilarMartínez-Piñeiro, LuisCuesta Martínez, ÁngelBotella, Luisa Maria2023-12-212023-12-212020Albiñana V, Gallardo-Vara E, de Rojas-P I, Recio-Poveda L, Aguado T, Canto-Cano A, Aguirre DT, Serra MM, González-Peramato P, Martínez-Piñeiro L, Cuesta AM, Botella LM. Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel-Lindau Disease. J Clin Med. 2020 Aug 25;9(9):274010.3390/jcm9092740https://hdl.handle.net/20.500.14352/91712Von 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2077-0383https://doi.org/10.3390/jcm9092740open access577.175.8615.361.45616-006.04-02β-adrenergic receptor antagonistICI-118,551PropranololHIFVHLAnticarcinogenicBioquímica (Biología)Oncología2403 Bioquímica3207.03 Carcinogénesis3207.13 Oncología