摘要
甲状旁腺肿瘤与由于甲状旁腺素(PTH)分泌过多而导致的原发性(PHPT)或继发性(SHPT)甲状旁腺功能亢进有关。亢进症(PHPT)是三个最常见的内分泌紊乱疾病之一,其中绝经后妇女患病率为1-2%;SHPT是慢性肾功能衰竭的主要并发症,其发病率正在增加。钙敏感受体(CASR)是调节PTH合成的关键分子,并从甲状旁腺细胞释放,而甲状旁腺细胞因细胞外钙浓度变化产生响应。西那卡塞,一个强效拟钙剂,过去十年的发展,可为PHPT和SHPT提供药物治疗。在有不同严重程度的PHPT和SHPT患者,包括甲状旁腺癌和与MEN1相关甲状旁腺肿瘤患者治疗中,西那卡塞已被证明能有效地抑制PTH分泌,虽然其未能使PTH释放正常化。本文研究CASR靶向治疗的分子方面和CASR基因单核苷酸多态性的效果。关于西那卡塞在控制甲状旁腺功能亢进症的疗效和安全性方面已有临床数据报道,且专注于不同类型甲状旁腺肿瘤的治疗作用。最后,对靶向治疗的局限性进行了分析,指出了其在改善PHPT中肾脏和骨骼并发症及SHPT中心血管疾病方面疗效并不理想。虽然西那卡塞为甲状旁腺肿瘤提供靶向治疗,但完全控制代谢紊乱和潜在肿瘤还需进一步进行方法学研究。
关键词: 钙敏感受体,甲状旁腺激素,甲状旁腺肿瘤,原发性甲状旁腺功能亢进,单核苷酸多态性。
Current Cancer Drug Targets
Title:Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Volume: 15 Issue: 7
Author(s): Alessandra Mingione, Chiara Verdelli, Annalisa Terranegra, Laura Soldati and Sabrina Corbetta
Affiliation:
关键词: 钙敏感受体,甲状旁腺激素,甲状旁腺肿瘤,原发性甲状旁腺功能亢进,单核苷酸多态性。
摘要: Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.
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Alessandra Mingione, Chiara Verdelli, Annalisa Terranegra, Laura Soldati and Sabrina Corbetta , Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors, Current Cancer Drug Targets 2015; 15 (7) . https://dx.doi.org/10.2174/1568009615666150602143041
DOI https://dx.doi.org/10.2174/1568009615666150602143041 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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