Division of Urology, Department of Surgery, University of Colorado at Denver, Health Sciences Center, School of Medicine, Aurora, CO 80045, USA.
Prostate Cancer Prostatic Dis. 2012 Jun;15(2):111-9. doi: 10.1038/pcan.2011.41. Epub 2011 Aug 30.
As a result of their ability to effectively reduce the risk of skeletal-related events, bisphosphonates (BPs) were incorporated into clinical practice over a decade ago, leading to a new treatment paradigm for patients with skeletal involvement from advanced cancer. BPs are now a well-established treatment option in this setting. Our review of the literature found that in addition to maintaining bone health in patients with malignant bone lesions and patients at risk for cancer therapy-induced bone loss, emerging preclinical and clinical data suggest that BPs may also have anticancer activity. Later generation, nitrogen-containing BPs (N-BPs), such as zoledronic acid (ZOL), inhibit the mevalonate pathway, subsequently inhibiting a number of cellular functions in bone-resorbing osteoclasts. In addition, N-BPs inhibit cancer cell proliferation, viability, motility, invasion and angiogenesis; induce cancer cell apoptosis; and act in synergy with antineoplastic agents. N-BPs, especially ZOL, may be useful as anticancer agents. As evidence continues to emerge, another shift in cancer treatment paradigms, in which N-BPs are considered for their anticancer activity as well as palliative effects, may be approaching.
由于其能够有效地降低骨骼相关事件的风险，双膦酸盐（BPs）在十多年前被纳入临床实践，为骨骼受晚期癌症累及的患者带来了新的治疗模式。BPs 现在是该领域的一种成熟的治疗选择。我们对文献的回顾发现，除了维持恶性骨病变患者和有癌症治疗引起的骨质流失风险的患者的骨骼健康外，新的临床前和临床数据表明，BPs 也可能具有抗癌活性。后来出现的含氮 BPs（N-BPs），如唑来膦酸（zoledronic acid，ZOL），抑制了甲羟戊酸途径，随后抑制了破骨细胞中许多与骨吸收相关的细胞功能。此外，N-BPs 抑制癌细胞的增殖、活力、迁移、侵袭和血管生成；诱导癌细胞凋亡；并与抗肿瘤药物协同作用。N-BPs，特别是 ZOL，可能作为抗癌药物有用。随着证据的不断涌现，癌症治疗模式可能会发生另一个转变，即将 N-BPs 用于其抗癌活性和姑息治疗效果。
