Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
J Bone Miner Metab. 2021 Jan;39(1):71-81. doi: 10.1007/s00774-020-01182-2. Epub 2021 Jan 2.
Bone metastasis involves tumor-induced osteoclast activation, resulting in skeletal tumor progression as well as skeletal disorders. Aberrant expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for osteoclast differentiation, induced by the metastatic tumor cells is responsible for the pathological bone resorption in bone metastasis. A fully human anti-RANKL neutralizing antibody has been developed to block osteoclast activation and is now used for the treatment of patients with bone metastasis and multiple myeloma. On the other hand, numerous studies have revealed that the RANKL/RANK system also contributes to primary tumorigenesis as well as metastasis through osteoclast-independent processes. Furthermore, emerging clinical and preclinical evidence has suggested anti-tumor immune effects of RANKL blockade when added to immune checkpoint inhibitor therapies. Study on the pleiotropic functions of RANKL in tumorigenesis and metastasis is now expanding beyond the bone field and has been established as one of the most important areas of "RANKL biology".
骨转移涉及肿瘤诱导的破骨细胞激活，导致骨骼肿瘤进展和骨骼疾病。转移瘤细胞异常表达核因子-κB 配体受体激活剂（RANKL），这是破骨细胞分化所必需的细胞因子，导致骨转移中的病理性骨吸收。一种完全人源化的抗 RANKL 中和抗体已被开发出来以阻断破骨细胞激活，目前用于治疗骨转移和多发性骨髓瘤患者。另一方面，大量研究表明，RANKL/RANK 系统也通过破骨细胞独立的过程促进原发性肿瘤发生和转移。此外，新兴的临床前和临床证据表明，在免疫检查点抑制剂治疗中加入 RANKL 阻断具有抗肿瘤免疫作用。目前，关于 RANKL 在肿瘤发生和转移中的多效性功能的研究已经超出了骨骼领域，并已成为“RANKL 生物学”的最重要领域之一。
