Institut National de la Santeet de la Recherche Medicale, Research Unit UMR 1033, Facultede Medecine Lyon-Est (domaine Laennec), 8 Rue Guillaume Paradin, F-69372 Lyon, France.
Anticancer Agents Med Chem. 2012 Feb;12(2):102-13. doi: 10.2174/187152012799014977.
Bone is a common site of metastasis from advanced cancers, and metastasis to bone accounts for the majority of distant recurrences from breast and prostate cancers. Bone metastases are characterized by increased rates of bone turnover. Bisphosphonates are extensively used in the treatment of metastatic bone disease to reduce the rates of osteolysis and the risk of skeletal-related events. In addition, bisphosphonates have demonstrated direct and indirect anticancer potential in preclinical studies. These activities include induction of apoptosis, inhibition of invasion, synergistic cytotoxicity with chemotherapy agents, antiangiogenic properties, and modulation of immunologic activity against transformed cells. Notably, these activities of bisphosphonates are not limited to the bone microenvironment; indeed some effects are mediated on the cancer cells themselves. These preclinical data provide the rationale for the underlying potential clinical benefits from bisphosphonates (e.g., prevention of metastasis to bone and other sites in the early breast cancer setting and delayed disease progression in malignancies involving colonization of bone [e.g., multiple myeloma]). This review article summarizes the preclinical anticancer activities of bisphosphonates in various cancer types and evaluates their potential contributions to the recently demonstrated clinical effects.
骨骼是晚期癌症转移的常见部位，而乳腺癌和前列腺癌的远处复发大多与骨转移有关。骨转移的特征是骨转换率增加。双膦酸盐广泛用于治疗转移性骨疾病，以降低溶骨性和骨骼相关事件的风险。此外，双膦酸盐在临床前研究中表现出直接和间接的抗癌潜力。这些活动包括诱导细胞凋亡、抑制侵袭、与化疗药物协同细胞毒性、抗血管生成特性以及调节对转化细胞的免疫活性。值得注意的是，这些双膦酸盐的活性不仅限于骨微环境；实际上，一些作用是在癌细胞本身中介导的。这些临床前数据为双膦酸盐的潜在临床益处提供了依据（例如，在早期乳腺癌环境中预防骨转移和其他部位的转移，以及在涉及骨骼定植的恶性肿瘤中延迟疾病进展[例如多发性骨髓瘤]）。本文综述了双膦酸盐在各种癌症类型中的临床前抗癌活性，并评估了它们对最近显示的临床效果的潜在贡献。
