Corso Alessandro, Ferretti Eleonora, Lazzarino Mario
Division of Hematology, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Hematology. 2005 Jun;10(3):215-24. doi: 10.1080/10245330500094714.
Multiple myeloma (MM) is a B-cell malignancy characterized by an excess of monotypic plasma cells which localize almost exclusively in the bone marrow provoking bone destruction via the activation of the osteoclasts. The bone marrow microenvironment, mainly through stromal cells, is strictly involved in the evolution of the disease supporting MM cell growth and survival [1]. MM plasma cells reside in the bone marrow by binding to adhesion molecule of extracellular matrix (ECM) and stromal cells. The activation of some signaling pathways within the stromal cells increases the production of several cytokines which in turn favors the myeloma cell proliferation and survival [2-6], and enhance the drug resistance by anti-apoptotic mechanisms [1,7-9]. Novel therapeutic agents target not only the myeloma cells but also the interaction between MM cells and the bone marrow microenvironment [8]. Bisphosphonates (Bps) interfere as well with bone microenvironment inhibiting the survival of stromal cells and hampering the contact between plasma and stromal cells. In this review we will revise preclinical evidences, and the potential mechanisms of the antitumor activity of zoledronic acid.
多发性骨髓瘤（MM）是一种B细胞恶性肿瘤，其特征是单克隆浆细胞过多，这些浆细胞几乎仅定位于骨髓，通过激活破骨细胞引发骨质破坏。骨髓微环境，主要通过基质细胞，严格参与支持MM细胞生长和存活的疾病演变过程[1]。MM浆细胞通过与细胞外基质（ECM）和基质细胞的黏附分子结合而驻留在骨髓中。基质细胞内某些信号通路的激活会增加几种细胞因子的产生，进而促进骨髓瘤细胞的增殖和存活[2-6]，并通过抗凋亡机制增强耐药性[1,7-9]。新型治疗药物不仅靶向骨髓瘤细胞，还靶向MM细胞与骨髓微环境之间的相互作用[8]。双膦酸盐（Bps）也会干扰骨微环境，抑制基质细胞的存活并阻碍浆细胞与基质细胞之间的接触。在本综述中，我们将回顾唑来膦酸抗肿瘤活性的临床前证据及其潜在机制。
