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Wnt/β-catenin 信号通路在肾上腺皮质癌肿瘤进展中的作用。

Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma.

机构信息

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Taiyuan, China.

Department of Ambulatory Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Front Endocrinol (Lausanne). 2024 Jan 9;14:1260701. doi: 10.3389/fendo.2023.1260701. eCollection 2023.

Abstract

Adrenocortical carcinoma (ACC) is an uncommon, aggressive endocrine malignancy with a high rate of recurrence, a poor prognosis, and a propensity for metastasis. Currently, only mitotane has received certification from both the US Food and Drug Administration (FDA) and the European Medicines Agency for the therapy of advanced ACC. However, treatment in the advanced periods of the disorders is ineffective and has serious adverse consequences. Completely surgical excision is the only cure but has failed to effectively improve the survival of advanced patients. The aberrantly activated Wnt/β-catenin pathway is one of the catalysts for adrenocortical carcinogenesis. Research has concentrated on identifying methods that can prevent the stimulation of the Wnt/β-catenin pathway and are safe and advantageous for patients in view of the absence of effective treatments and the frequent alteration of the Wnt/β-catenin pathway in ACC. Comprehending the complex connection between the development of ACC and Wnt/β-catenin signaling is essential for accurate pharmacological targets. In this review, we summarize the potential targets between adrenocortical carcinoma and the Wnt/β-catenin signaling pathway. We analyze the relevant targets of drugs or inhibitors that act on the Wnt pathway. Finally, we provide new insights into how drugs or inhibitors may improve the treatment of ACC.

摘要

肾上腺皮质癌(ACC)是一种罕见的、侵袭性的内分泌恶性肿瘤,具有较高的复发率、预后不良和转移倾向。目前,只有米托坦(mitotane)获得了美国食品和药物管理局(FDA)和欧洲药品管理局(EMA)的认证,可用于治疗晚期 ACC。然而,对于晚期疾病的治疗是无效的,并且有严重的不良后果。完全手术切除是唯一的治愈方法,但未能有效改善晚期患者的生存。异常激活的 Wnt/β-连环蛋白途径是导致肾上腺皮质癌发生的催化剂之一。鉴于缺乏有效的治疗方法以及 ACC 中 Wnt/β-连环蛋白途径的频繁改变,研究集中于寻找可以阻止 Wnt/β-连环蛋白途径刺激且对患者安全有利的方法。理解 ACC 的发展与 Wnt/β-连环蛋白信号之间的复杂联系对于准确的药理靶点至关重要。在这篇综述中,我们总结了肾上腺皮质癌与 Wnt/β-连环蛋白信号通路之间的潜在靶点。我们分析了作用于 Wnt 通路的药物或抑制剂的相关靶点。最后,我们提供了新的见解,说明药物或抑制剂如何改善 ACC 的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6861/10806569/eb182e381d91/fendo-14-1260701-g001.jpg

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