Pereira Sofia S, Oliveira Sofia, Monteiro Mariana P, Pignatelli Duarte
Department of Anatomy, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal.
Clinical and Experimental Endocrinology, Multidisciplinary Unit for Biomedical Research (UMIB), 4050-313 Porto, Portugal.
Cancers (Basel). 2021 Mar 1;13(5):1030. doi: 10.3390/cancers13051030.
Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed.
血管生成在多种生理和病理过程中发挥着重要作用。药理学上对血管生成的调节已被充分证明在多种癌症中可实现临床益处。肾上腺皮质癌（ACC）是一种罕见的肿瘤，其预后通常较差。此外，ACC的治疗选择有限。了解在胚胎发育过程中和ACC中调节肾上腺皮质血管生成的机制，可为如何通过药理学方法调节这些过程以治疗ACC提供重要线索。在本报告中，我们对生理条件下和ACC中的肾上腺皮质血管生成调节进行了综合综述。在胚胎发育过程中，肾上腺血管生成受VEGF和Ang-Tie信号通路的调节。在ACC中，早期的研究工作集中在VEGF信号通路，该通路被确定为一个良好的预后因素，因此是一个有前景的治疗靶点。然而，迄今为止在ACC中单独或联合使用靶向VEGF通路的药物进行的每一项临床试验都产生了令人失望的结果。相比之下，尽管Ang-Tie通路已被指出是胎儿肾上腺皮质血管生成的重要调节因子，但其在ACC中的作用尚待探索。未来，需要进一步研究调节Ang-Tie和VEGF通路在ACC中的作用和疗效。
