Cancer-induced bone disease greatly diminishes the quality of life for patients with bone metastatic breast cancer, resulting in painful skeletal-related events including bone loss and fracture. Improved understanding of the roles of osteoblasts and osteoclasts, and how tumors alter their biology, has led to blockbuster therapies that significantly reduce skeletal-related events, but the disease remains incurable. However, emerging technologies and tools for studying the role of other stromal and immune components in controlling tumor–host interactions have begun to reveal new insights that may yield tractable therapeutic targets to further mitigate the painful effects of bone metastases. In this issue of Cancer Research, Kaur and colleagues study osteocytes, which are terminally differentiated osteoblasts and entombed within the bone matrix, from established bone metastatic breast cancer and report how the disease ages them as characterized by a senescence-associated secretory phenotype. This premature development of osteocyte senescence in turn enhances bone destruction and osteoclastogenic potential. Targeting senescent cells using senolytics suppressed bone resorption and preserved bone mass. Collectively, these findings underscore osteocyte involvement in the “vicious cycle” of bone metastasis, and targeting senescent osteocytes represents a new avenue for managing cancer-induced bone disease.See related article by Kaur et al., p. 3936

中文翻译：

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衰老骨细胞隐窝癌症诱导的骨病故事


癌症诱发的骨病大大降低了骨转移性乳腺癌患者的生活质量，导致痛苦的骨骼相关事件，包括骨质流失和骨折。对成骨细胞和破骨细胞的作用以及肿瘤如何改变其生物学特性的理解的提高，导致了重磅疗法的出现，这些疗法显着减少了骨骼相关事件，但这种疾病仍然无法治愈。然而，用于研究其他基质和免疫成分在控制肿瘤-宿主相互作用中的作用的新兴技术和工具已经开始揭示新的见解，这些见解可能会产生易于处理的治疗靶点，以进一步减轻骨转移的痛苦影响。在本期《癌症研究》中，Kaur 及其同事研究了来自已确诊的骨转移性乳腺癌的骨细胞，这些骨细胞是终末分化的成骨细胞，埋藏在骨基质中，并报告了该疾病如何使它们衰老，其特征是衰老相关的分泌表型。这种骨细胞衰老的过早发展反过来又增强了骨破坏和破骨细胞生成潜力。使用 senolytics 靶向衰老细胞可抑制骨吸收并保留骨量。总的来说，这些发现强调了骨细胞参与骨转移的“恶性循环”，靶向衰老的骨细胞代表了管理癌症诱导的骨病的新途径。参见 Kaur 等人的相关文章，第 3936 页