Department of Biochemistry and Biophysics, II University of Naples, Via Costantinopoli no16, 80138 Naples, Itlay.
Curr Cancer Drug Targets. 2009 Nov;9(7):791-800. doi: 10.2174/156800909789760285.
Therapy with aminobisphosphonate (N-BPs), and zoledronic acid (ZOL) especially, has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that N-BPs exert their direct or indirect anti-tumour effects on cancer growth factor release, cancer cell adhesion, invasion and viability, cancer angiogenesis and cancer cell apoptosis. Here, we will discuss the molecular mechanisms of the antitumour effects induced by ZOL. Despite their well-established in vitro anti-tumour effects N-BPs have not clear in vivo anti-tumour activity in humans. The bases of these discrepancies will be discussed in the text with a special focus on the pharmacokinetic limits of N-BPs. Moreover, the following molecular and pharmacological strategies in order to overcome N-BPs limitations will be described: i) development of pharmacological combinations with other biological agents; ii) finding of new molecular targets of N-BPs; iii) development of new pharmacological formulations of N-BPs. Finally, a new scenario of integrated bio-medicine and pharmacology will be depicted in order to drive the optimization of anti-cancer activity of N-BPs.
用氨膦酸盐（N-BPs），特别是唑来膦酸（ZOL）进行治疗，已经成为恶性骨病患者的标准治疗方法。此外，临床前和初步临床数据表明，N-BPs 通过释放肿瘤生长因子、癌细胞黏附、侵袭和活力、癌症血管生成和癌细胞凋亡来发挥其直接或间接的抗肿瘤作用。在这里，我们将讨论 ZOL 诱导的抗肿瘤作用的分子机制。尽管 N-BPs 在体外具有明确的抗肿瘤作用，但在体内对人类的抗肿瘤活性并不明确。本文将讨论这些差异的基础，并特别关注 N-BPs 的药代动力学限制。此外，还将描述以下克服 N-BPs 局限性的分子和药理学策略：i）开发与其他生物制剂的药理学组合；ii）寻找 N-BPs 的新分子靶点；iii）开发 N-BPs 的新药理制剂。最后，将描绘一个新的综合生物医学和药理学场景，以推动 N-BPs 抗癌活性的优化。
