Brodowicz Thomas, Hemetsberger Margit, Windhager Reinhard
Department of Internal Medicine 1/Oncology, Comprehensive Cancer Center Vienna, MusculoSkeletal Tumor Unit, Medical University Vienna, Vienna, Austria.
Hemetsberger Medical Services, Vienna, Austria.
Future Oncol. 2015;11(13):1881-94. doi: 10.2217/fon.15.94.
Giant cell tumor of bone is typically composed of neoplastic stromal cells and non-neoplastic osteoclastic giant cells. RANK-expressing osteoclastic giant cells are recruited by RANK ligand excreted by the stromal cells, and used by these neoplastic cells to create expansion space. Denosumab specifically binds to and inhibits RANK ligand, thereby eradicating osteoclastic giant cells from the tumor and thus reducing osteolytic activity. Clinical studies reported disease stabilization and clinical benefit in terms of reduced pain and analgesics use, avoided surgeries or surgeries with less morbid procedures. Adverse events observed in patients with giant cell tumor of bone were consistent with the known safety profile of denosumab with a very low incidence of hypocalcemia and osteonecrosis. Overall, denosumab was shown to suppress osteolytic activity and slow disease progression and is thus a treatment option for patients with giant cell tumor of bone.
骨巨细胞瘤通常由肿瘤性基质细胞和非肿瘤性破骨细胞样巨细胞组成。表达RANK的破骨细胞样巨细胞被基质细胞分泌的RANK配体招募,并被这些肿瘤细胞用来创造扩张空间。地诺单抗特异性结合并抑制RANK配体,从而从肿瘤中清除破骨细胞样巨细胞,进而降低骨溶解活性。临床研究报告称,疾病得到稳定,在减轻疼痛和减少镇痛药使用、避免手术或采用创伤较小的手术方面具有临床益处。在骨巨细胞瘤患者中观察到的不良事件与地诺单抗已知的安全性特征一致,低钙血症和骨坏死的发生率非常低。总体而言,地诺单抗被证明可抑制骨溶解活性并减缓疾病进展,因此是骨巨细胞瘤患者的一种治疗选择。