University of Miami, Deerfield Beach, FL 33442, USA.
Clin Breast Cancer. 2010 Oct 1;10(5):359-66. doi: 10.3816/CBC.2010.n.047.
Bisphosphonates (BPs) are approved for preventing the skeletal-related events associated with malignant bone disease. Several studies indicate that they may also prevent cancer therapy-induced bone loss. Multiple preclinical and early clinical studies provide evidence of the anticancer activity of BPs, including an inhibition of tumor cell proliferation and survival, a reduction of angiogenesis, and a stimulation of innate anticancer immunity. In addition to their evident single-agent activity, BPs may also act synergistically with other antineoplastic agents. Translational studies corroborate the effects of bisphosphonates on angiogenesis and innate immunity. Moreover, many of these anticancer effects occur at clinically relevant drug concentrations. Indeed, clinical data suggest that in addition to being well-tolerated and efficacious in maintaining bone health, BPs including clodronate, pamidronate, and zoledronic acid also improve cancer-related outcomes such as tumor response, disease-free survival, and overall survival in patients with breast cancer. Among the BPs, zoledronic acid is the most extensively studied in the adjuvant and neoadjuvant settings and has accumulated the most data pointing to anticancer activity, although a survival benefit has not been documented. Future studies are necessary to elucidate the anticancer activity of BPs. Other aspects of BP therapy that require further study include the optimization of dosing regimens for single agents and combinations in various clinical settings and the identification of prognostic factors that predict treatment outcomes. This review summarizes the preclinical and clinical evidence of anticancer activity of BPs, with a focus on zoledronic acid.
双膦酸盐（BPs）被批准用于预防与恶性骨病相关的骨骼相关事件。多项研究表明，它们还可能预防癌症治疗引起的骨丢失。多项临床前和早期临床研究提供了 BPs 抗癌活性的证据，包括抑制肿瘤细胞增殖和存活、减少血管生成和刺激固有抗癌免疫。除了明显的单一药物活性外，BPs 还可能与其他抗肿瘤药物协同作用。转化研究证实了 BPs 对血管生成和固有免疫的影响。此外，这些抗癌作用中的许多在临床上相关的药物浓度下发生。事实上，临床数据表明，除了在维持骨骼健康方面具有良好的耐受性和疗效外，包括氯膦酸盐、帕米膦酸盐和唑来膦酸在内的 BPs 还可改善乳腺癌患者的癌症相关结局，如肿瘤反应、无病生存期和总生存期。在 BPs 中，唑来膦酸在辅助和新辅助环境中研究最广泛，积累的数据最多，表明其具有抗癌活性，尽管尚未证明有生存获益。需要进一步的研究来阐明 BPs 的抗癌活性。BP 治疗的其他方面也需要进一步研究，包括优化单一药物和联合治疗在各种临床环境中的剂量方案，以及确定预测治疗结果的预后因素。本综述总结了 BPs 的临床前和临床抗癌活性证据，重点是唑来膦酸。
