Brozovich Ava, Garmezy Benjamin, Pan Tianhong, Wang Liyun, Farach-Carson Mary C, Satcher Robert L
Texas A&M College of Medicine, Bryan, TX, USA.
Department of Regenerative Medicine, Houston Methodist Research Institute, Houston, TX, USA.
J Bone Oncol. 2021 Oct 20;31:100399. doi: 10.1016/j.jbo.2021.100399. eCollection 2021 Dec.
Renal cell carcinoma (RCC) is the most common malignancy of the kidney, representing 80-90% of renal neoplasms, and is associated with a five-year overall survival rate of approximately 74%. The second most common site of metastasis is bone. As patients are living longer due to new RCC targeting agents and immunotherapy, RCC bone metastases (RCCBM) treatment failure is more prevalent. Bone metastasis formation in RCC is indicative of a more aggressive disease and worse prognosis. Osteolysis is a prominent feature and causes SRE, including pathologic fractures. Bone metastasis from other tumors such as lung, breast, and prostate cancer, are more effectively treated with bisphosphonates and denosumab, thereby decreasing the need for palliative surgical intervention. Resistance to these antiresportives in RCCBM reflects unique cellular and molecular mechanisms in the bone microenvironment that promote progression via inhibition of the anabolic reparative response. Identification of critical mechanisms underlying RCCBM induced anabolic impairment could provide needed insight into how to improve treatment outcomes for patients with RCCBM, with the goals of minimizing progression that necessitates palliative surgery and improving survival.
肾细胞癌（RCC）是最常见的肾脏恶性肿瘤，占肾脏肿瘤的80-90%，其五年总生存率约为74%。第二常见的转移部位是骨骼。由于新型RCC靶向药物和免疫疗法的出现，患者的生存期延长，RCC骨转移（RCCBM）治疗失败的情况更为普遍。RCC中骨转移的形成表明疾病更具侵袭性且预后更差。骨溶解是一个突出特征，并会导致骨相关事件（SRE），包括病理性骨折。对于来自其他肿瘤（如肺癌、乳腺癌和前列腺癌）的骨转移，使用双膦酸盐和地诺单抗治疗更为有效，从而减少了姑息性手术干预的需求。RCCBM对这些抗骨吸收药物的耐药性反映了骨微环境中独特的细胞和分子机制，这些机制通过抑制合成代谢修复反应促进疾病进展。确定RCCBM诱导的合成代谢损伤的关键机制，有助于深入了解如何改善RCCBM患者的治疗效果，目标是尽量减少需要姑息性手术的病情进展并提高生存率。
