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oai:docta.ucm.es:20.500.14352/917122024-08-30T00:09:23Zcom_20.500.14352_14col_20.500.14352_15

Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease 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 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 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. Ministerio de Economía y Competitividad (España) Comunidad de Madrid Alianza Española de Familias van Hippel-Lindau Centro de Investigación Biomédica en Red de Enfermedades Raras European Commission Depto. de Bioquímica y Biología Molecular Fac. de Ciencias Biológicas TRUE pub 2023-12-21T12:56:07Z 2023-12-21T12:56:07Z 2020 journal article VoR https://hdl.handle.net/20.500.14352/91712 XXXX-XXXX 10.3390/jcm9092740 2077-0383 eng (SAF2017-83351-R. L.M-P) “IMMUNOTHERCAN” [B2017/BMD-3733-2] Albiñana 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):2740 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf MDPI