Dickerson Erin B, Bryan Brad A
Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, MN 55108, USA.
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN 55108, USA.
Vet Sci. 2015 Sep 21;2(3):270-292. doi: 10.3390/vetsci2030270.
Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains dismal for both humans and dogs, and each is likely to succumb to their disease within a short duration. While angiosarcomas in humans are extremely rare, limiting their study and treatment options, canine hemangiosarcomas occur frequently. Therefore, studies of these sarcomas in dogs can be used to advance treatment approaches for both patient groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize beta adrenergic signaling to drive their progression by regulating the tumor cell niche and fine-tuning cellular responses within the tumor microenvironment. These discoveries indicate that inhibition of beta adrenergic signaling could serve as an Achilles heel for these tumors and emphasize the need to design therapeutic strategies that target tumor cell and stromal cell constituents. In this review, we summarize recent discoveries and present new hypotheses regarding the roles of beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use of beta adrenergic receptor antagonists is well established in human and veterinary medicine, beta blockade could provide an immediate adjunct therapy for treatment along with a tangible opportunity to improve upon the outcomes of both humans and dogs with these diseases.
人类血管肉瘤和犬血管肉瘤是极具侵袭性的癌症，被认为起源于血管源性细胞。犬血管肉瘤的病理特征、形态结构和临床行为与人类血管肉瘤几乎没有区别。对于人类和犬类而言，采用当前的标准治疗方法，总体生存率仍然很低，而且两者都可能在短时间内死于该疾病。虽然人类血管肉瘤极为罕见，限制了对其的研究和治疗选择，但犬血管肉瘤却很常见。因此，对犬类这些肉瘤的研究可用于推进针对这两类患者群体的治疗方法。新出现的数据表明，血管肉瘤和血管肉瘤利用β肾上腺素能信号传导，通过调节肿瘤细胞生态位和微调肿瘤微环境中的细胞反应来推动其进展。这些发现表明，抑制β肾上腺素能信号传导可能是这些肿瘤的致命弱点，并强调需要设计针对肿瘤细胞和基质细胞成分的治疗策略。在本综述中，我们总结了最近的发现，并提出了关于β肾上腺素能信号传导在血管肉瘤和血管肉瘤中作用的新假设。由于β肾上腺素能受体拮抗剂在人类和兽医学中已得到广泛应用，β受体阻滞剂可为治疗提供即时辅助治疗，同时也为改善患有这些疾病的人类和犬类的治疗结果提供切实机会。
