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BONE METASTASES IN NEUROENDOCRINE TUMORS: MOLECULAR PATHOGENESIS AND IMPLICATIONS IN CLINICAL PRACTICE.
Neuroendocrinology ( IF 3.2 ) Pub Date : 2020-05-13 , DOI: 10.1159/000508633
Mauro Cives 1 , Eleonora Pellè 2 , Maria Rinzivillo 3 , Daniela Prosperi 4 , Marco Tucci 2 , Franco Silvestris 2 , Francesco Panzuto 3
Affiliation  

Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report an incidence of bone metastases as high as 20% in subjects with advanced disease. While the biologic mechanisms leading to bone metastatic colonization in NETs have been poorly investigated so far, key steps of osteotropic mechanisms including the epithelial-to-mesenchymal transition, preparation of the pre-metastatic niche, migration of circulating tumor cells towards the bone marrow as well as the resulting alterations of the skeletal metabolism, are likely to operate also during the development of NET bone metastases. The skeleton involvement by NETs has a detrimental impact on both quality of life and patients' prognosis, leading to pain in the majority of symptomatic subjects. While it is currently unclear whether or not the earlier recognition of bone involvement by PET/CT imaging techniques employing 68Ga-DOTA-conjugated peptides might improve outcomes through the exploitation of timely treatments, the management of bone-colonizing NETs is today based only on clinical experience from other osteotropic tumors. Here, we summarize the fundamental molecular mechanisms driving bone colonization and revisit both established and novel treatments for patients with bone metastatic NETs.


中文翻译:

神经内分泌肿瘤中的骨转移:分子发病机制和临床实践的意义。

骨骼定植通常被认为是神经内分泌肿瘤 (NETs) 患者的罕见事件,尽管国家注册和回顾性系列报告显示晚期疾病患者骨转移的发生率高达 20%。虽然迄今为止导致 NET 中骨转移定植的生物学机制研究得很少,但骨细胞机制的关键步骤包括上皮-间充质转化、转移前生态位的准备、循环肿瘤细胞向骨髓的迁移作为以及由此产生的骨骼代谢改变,也可能在 NET 骨转移的发展过程中起作用。NETs 的骨骼参与对生活质量和患者的预后都有不利影响,导致大多数有症状的受试者疼痛。虽然目前尚不清楚使用 68Ga-DOTA 偶联肽的 PET/CT 成像技术早期识别骨骼受累是否可以通过及时治疗来改善结果,但如今对骨定植 NET 的管理仅基于临床其他骨肿瘤的经验。在这里,我们总结了驱动骨定植的基本分子机制,并重新审视了骨转移性 NET 患者的既定治疗方法和新型治疗方法。如今,骨定植 NET 的管理仅基于其他骨肿瘤的临床经验。在这里,我们总结了驱动骨定植的基本分子机制,并重新审视了骨转移性 NET 患者的既定治疗方法和新型治疗方法。如今,骨定植 NET 的管理仅基于其他骨肿瘤的临床经验。在这里,我们总结了驱动骨定植的基本分子机制,并重新审视了骨转移性 NET 患者的既定治疗方法和新型治疗方法。
更新日期:2020-05-13
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