Antitumor effects of bisphosphonates: Promising preclinical evidence
Antitumor effects of bisphosphonates: Promising preclinical evidence
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DOI：
10.1016/j.ctrv.2008.03.006
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发表时间：
2008-01-01
影响因子：
11.8
通讯作者：
Guise, Theresa A.
中科院分区：
文献类型：
--
作者：
Guise, Theresa A.
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，这增加了虚弱和潜在限制生命的短暂性事件的风险。因此，制定适当的策略来预防骨转移是至关重要的。用于治疗和预防多发性骨髓瘤和继发于实体瘤的骨转移引起的骨骼相关事件的双膦酸盐，也可能具有直接和间接的抗肿瘤作用。来自体外和体内临床前研究的新证据。对几种肿瘤类型的研究表明，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性能似乎可以直接阻止肿瘤细胞的生长和血管生成；此外，将双膦酸盐与细胞毒性化疗相结合可能会提供进一步的抗肿瘤协同作用。在体外连续应用细胞毒性化疗(如阿霉素、紫杉醇和吉西他滨)和双膦酸类药物比单独使用这两种药物诱导更多的肿瘤细胞凋亡，并有效地抑制体内肿瘤的生长。此外，活体数据表明，优化给药程序可能会显著提高存活率。总体而言，临床前。数据表明，双膦酸盐具有抗肿瘤潜力，前景看好，并为正在进行的几项临床研究提供了动力。(C)2008年，爱思唯尔有限公司出版。
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 sketetal-retated 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. (c) 2008 Published by Elsevier Ltd.