Department of Pediatric Hematology-Oncology, Meyer Children's Hospital IRCCS, 50139 Florence, Italy.
Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy.
Biomolecules. 2024 Jan 29;14(2):159. doi: 10.3390/biom14020159.
Since the first discovery in 1989, the β3-adrenoceptor (β3-AR) has gained great attention because it showed the ability to regulate many physiologic and metabolic activities, such as thermogenesis and lipolysis in brown and white adipose tissue, respectively (BAT, WAT), negative inotropic effects in cardiomyocytes, and relaxation of the blood vessels and the urinary bladder. The β3-AR has been suggested as a potential target for cancer treatment, both in adult and pediatric tumors, since under hypoxia its upregulation in the tumor microenvironment (TME) regulates stromal cell differentiation, tumor growth and metastases, signifying that its agonism/antagonism could be useful for clinical benefits. Promising results in cancer research have proposed the β3-AR being targeted for the treatment of many conditions, with some drugs, at present, undergoing phase II and III clinical trials. In this review, we report the scientific journey followed by the research from the β3-Ars' discovery, with focus on the β3-Ars' role in cancer initiation and progression that elects it an intriguing target for novel antineoplastic approaches. The overview highlights the great potential of the β3-AR, both in physiologic and pathologic conditions, with the intention to display the possible benefits of β3-AR modulation in cancer reality.
自 1989 年首次发现以来，β3-肾上腺素能受体（β3-AR）因其能够调节棕色和白色脂肪组织（BAT、WAT）中的产热和脂肪分解等许多生理和代谢活动、心肌细胞中的负性肌力作用以及血管和膀胱的松弛而备受关注。由于缺氧时肿瘤微环境（TME）中β3-AR 的上调调节基质细胞分化、肿瘤生长和转移，β3-AR 被认为是成人和儿科肿瘤治疗的潜在靶点，其激动剂/拮抗剂可能对临床有益。癌症研究中的有前途的结果提出了针对许多疾病的β3-AR 靶向治疗，目前一些药物正在进行 II 期和 III 期临床试验。在这篇综述中，我们报告了β3-Ars 发现后的科学历程，重点介绍了β3-Ars 在癌症起始和进展中的作用，使其成为新型抗肿瘤方法的一个有趣靶点。该综述强调了β3-AR 在生理和病理条件下的巨大潜力，旨在展示β3-AR 调节在癌症现实中的可能益处。
