Guise Theresa A
Division of Endocrinology, Department of Medicine, University of Virginia, Aurbach Medical Research Building, PO Box 801419, Charlottesville, VA 22903, United States.
Cancer Treat Rev. 2008;34 Suppl 1:S19-24. doi: 10.1016/j.ctrv.2008.03.006. Epub 2008 May 16.
The majority of patients with advanced cancer will ultimately develop bone metastases. The bone microenvironment provides fertile soil for a cycle of tumor growth and bone destruction that increases the risk of debilitating and potentially life-limiting skeletal-related events. Therefore, developing appropriate strategies to prevent bone metastases is critical. Bisphosphonates used to treat and prevent skeletal-related events resulting from multiple myeloma and bone metastases secondary to solid tumors, may also have direct and indirect antitumor effects. Emerging evidence from in vitro and in vivo preclinical studies in several tumor types suggests that bisphosphonates can reduce tumor burden in bone and soft tissue, inhibit angiogenesis, prevent tumor cell invasion and adhesion in bone, and induce tumor cell apoptosis. The powerful antiresorptive properties of bisphosphonates appear to directly prevent tumor cell growth and angiogenesis; in addition, combining bisphosphonates with cytotoxic chemotherapy may provide further antitumor synergies. Sequential application of cytotoxic chemotherapy (e.g., doxorubicin, paclitaxel, and gemcitabine) followed by bisphosphonates has been shown to induce significantly more tumor cell apoptosis than either agent alone in vitro and effectively inhibits tumor growth in vivo. Furthermore, in vivo data suggest that optimizing the dosing schedule may significantly increase survival. Overall, preclinical data suggesting that bisphosphonates have antitumor potential are promising and have provided the impetus for several ongoing clinical studies.
大多数晚期癌症患者最终会发生骨转移。骨微环境为肿瘤生长和骨破坏的循环提供了肥沃的土壤，增加了导致衰弱和可能危及生命的骨相关事件的风险。因此，制定适当的策略来预防骨转移至关重要。用于治疗和预防由多发性骨髓瘤及实体瘤继发骨转移引起的骨相关事件的双膦酸盐，可能也具有直接和间接的抗肿瘤作用。来自几种肿瘤类型的体外和体内临床前研究的新证据表明，双膦酸盐可以减轻骨和软组织中的肿瘤负担，抑制血管生成，防止肿瘤细胞在骨中的侵袭和黏附，并诱导肿瘤细胞凋亡。双膦酸盐强大的抗吸收特性似乎直接阻止肿瘤细胞生长和血管生成；此外，将双膦酸盐与细胞毒性化疗联合使用可能会提供进一步的抗肿瘤协同作用。在体外，细胞毒性化疗药物（如阿霉素、紫杉醇和吉西他滨）序贯应用双膦酸盐已显示比单独使用任何一种药物诱导更多的肿瘤细胞凋亡，并在体内有效抑制肿瘤生长。此外，体内数据表明优化给药方案可能显著提高生存率。总体而言，临床前数据表明双膦酸盐具有抗肿瘤潜力，这很有前景，并为几项正在进行的临床研究提供了动力。
