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Breast Cancer: Rank Ligand Inhibition

机译:乳腺癌:抑制配体

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Breast cancer and bone health are closely linked. Early menopause induced by gonadotropin-releasing hormone analogues or chemotherapy as well as aromatase inhibitors reduce oestrogen levels, thereby causing cancer treatment-induced bone loss (CTIBL). Furthermore, bone metastases are commonly found in advanced disease. Current treatment options for bone lesions comprise systemic anti-tumour therapy, irradiation, surgery and bisphosphonates. The main mechanism of osteolysis, osteoclast activation, is induced by the RANK ligand and suppressed by osteoprotegerin (OPG). A human antibody targeting the RANK ligand, denosumab, had superior activity compared to OPG and was therefore further developed in the clinical setting. This article reviews clinical data on denosumab. Data were obtained by searching the Medline database and abstracts from the ASCO annual meeting, ASCO breast meeting, ECCO, ESMO, and the San Antonio Breast Cancer Symposium. Clinical trials have demonstrated that denosumab reduces markers of bone turnover, and suggest equal efficacy to bisphosphonates in reducing the rate of skeletal-related events. While overall fewer side effects were observed, a numerically increased rate of osteonecrosis of the jaw was reported. Denosumab was well tolerated, and clinical activity was similar to bisphosphonates in metastatic disease. Trials of denosumab in the prevention of CTIBL are ongoing.
机译:乳腺癌与骨骼健康息息相关。促性腺激素释放激素类似物或化学疗法以及芳香酶抑制剂诱导的更年期早期降低雌激素水平,从而导致癌症治疗引起的骨丢失(CTIBL)。此外,骨转移通常在晚期疾病中发现。当前用于骨损伤的治疗选择包括全身抗肿瘤治疗,放射线,手术和双膦酸盐。溶骨的主要机制是破骨细胞活化,是由RANK配体诱导的,并由骨保护素(OPG)抑制。与OPG相比,靶向RANK配体的人抗体denosumab具有更高的活性,因此在临床环境中得到了进一步开发。本文回顾了denosumab的临床数据。通过搜索Medline数据库和ASCO年会,ASCO乳腺会议,ECCO,ESMO和圣安东尼奥乳腺癌专题讨论会的摘要来获取数据。临床试验表明,地诺单抗可减少骨转换的标志物,并暗示与双膦酸盐在降低骨骼相关事件的发生率方面具有同等效力。虽然总体上观察到的副作用较少,但据报道颌骨坏死的发生率在数值上有所增加。地诺单抗具有良好的耐受性,在转移性疾病中临床活性与双膦酸盐相似。 denosumab预防CTIBL的试验正在进行中。

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