Medical Oncology, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100, Catanzaro, Italy
Curr Cancer Drug Targets. 2012 Sep;12(7):757-67. doi: 10.2174/156800912802429300.
Multiple myeloma (MM) represents a suitable disease to be treated with Molecularly targeted drugs (MTDs). MM clone aberrations affect signal transduction pathways controlling both proliferation and/or cell survival. Research findings on small drugs or monoclonal antibodies (mAb) against the components of these pathways are now available and related clinical trials in MM patients are rapidly growing up. Promising results have been recently obtained with AKT inhibitors (perifosine) and mTOR inhibitors (everolimus and temsirolimus). However, the activity of these agents used alone is still limited and can be strongly increased by their combination with other drugs such as bortezomib or dexamethasone. The present review will summarize the main signaling components that can be targeted by MTDs and the most important available results derived from the clinical trials based on their use. Another important issue in the treatment of MM is the control of the related bone disease. Two main strategies can be used: i) inhibition of bone resorption and ii) promotion of bone formation. Emerging clinical data suggest that specific MTDs are able to prolong survival not only for the prevention of the skeletal-related events but also for a direct or indirect effect on the proliferation and/or survival of MM cells. A summary on the main preclinical and clinical results in this setting will be provided. In conclusion, the use of MTD in the treatment of MM is a promising approach but still far from becoming a current indication: a new dawn is arising with still unpredictable results.
多发性骨髓瘤（MM）是一种适合用分子靶向药物（MTD）治疗的疾病。MM 克隆异常影响控制增殖和/或细胞存活的信号转导途径。目前已有关于这些途径成分的小分子药物或单克隆抗体（mAb）的研究结果，针对 MM 患者的相关临床试验也在迅速增加。AKT 抑制剂（perifosine）和 mTOR 抑制剂（everolimus 和 temsirolimus）最近取得了有希望的结果。然而，这些药物单独使用的活性仍然有限，可以通过与硼替佐米或地塞米松等其他药物联合使用来大大增强。本综述将总结可通过 MTD 靶向的主要信号转导成分，以及基于其使用的临床试验的最重要结果。在 MM 的治疗中，另一个重要问题是控制相关的骨疾病。可以使用两种主要策略：i）抑制骨吸收和 ii）促进骨形成。新兴的临床数据表明，特定的 MTD 不仅能够预防骨骼相关事件，而且能够直接或间接影响 MM 细胞的增殖和/或存活，从而延长生存时间。将提供该领域主要的临床前和临床结果摘要。总之，MTD 在 MM 治疗中的应用是一种很有前途的方法，但距离成为当前适应证还有很长的路要走：新的曙光正在出现，但结果仍不可预测。
