Mitsiades Constantine S, Mitsiades Nicholas S, Munshi Nikhil C, Richardson Paul G, Anderson Kenneth C
Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street Boston, MA 02115, USA.
Eur J Cancer. 2006 Jul;42(11):1564-73. doi: 10.1016/j.ejca.2005.12.025. Epub 2006 Jun 9.
The close relationship between the biological behaviour of malignant cells and the local microenvironment where they reside is a feature of diverse neoplasias. Multiple myeloma (MM) is considered a main disease model for the study of such interactions and the mechanisms that can lead to bone-related clinical complications, as well as the role of these interactions in attenuating the activity of conventional anti-MM therapeutics, such as dexamethasone and cytotoxic chemotherapeutics. This review focuses on recent progress in the study of interactions of MM cells with their local microenvironment. Major emphasis is placed on how bone marrow stromal cells (BMSCs) and other normal constituents of the bone marrow milieu promote, through cell adhesion- and cytokine-mediated mechanisms, the ability of MM cells to resist conventional anti-MM therapies. The review also addresses ongoing research into these mechanisms, which has already provided several new molecular targets and corresponding therapeutic strategies, such as the proteasome inhibitor bortezomib and thalidomide derivatives (e.g. lenalidomide), for the management of myeloma.
恶性细胞的生物学行为与其所处的局部微环境之间的密切关系是多种肿瘤形成的一个特征。多发性骨髓瘤（MM）被认为是研究此类相互作用以及导致骨相关临床并发症的机制，以及这些相互作用在减弱传统抗MM治疗药物（如地塞米松和细胞毒性化疗药物）活性方面作用的主要疾病模型。本综述重点关注MM细胞与其局部微环境相互作用研究的最新进展。主要强调骨髓基质细胞（BMSC）和骨髓微环境中的其他正常成分如何通过细胞黏附及细胞因子介导的机制，促进MM细胞抵抗传统抗MM治疗的能力。该综述还讨论了对这些机制的正在进行的研究，这些研究已经提供了几个新的分子靶点和相应的治疗策略，如蛋白酶体抑制剂硼替佐米和沙利度胺衍生物（如来那度胺），用于骨髓瘤的治疗。
