Yasui Hiroshi, Hideshima Teru, Richardson Paul G, Anderson Kenneth C
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Br J Haematol. 2006 Feb;132(4):385-97. doi: 10.1111/j.1365-2141.2005.05860.x.
Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies, and novel biologically based treatment approaches are urgently required. Recent studies demonstrate that various growth factors including interleukin (IL)-6, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), the tumour necrosis factor (TNF) family proteins, Wnt, and Notch family members play an important role in MM pathogenesis, and mediate tumour cell proliferation, drug resistance and migration in the bone marrow (BM) milieu. Targeting growth factors, therefore, represents a promising therapeutic strategy in MM. Novel agents inhibiting growth factor signalling cascades can target ligands, receptors, and/or downstream signalling cascade proteins in MM cells and the BM microenvironment. Combinations of these novel agents with conventional therapies may not only enhance cytotoxicity, but also avoid drug resistance and thereby improve patient outcome in MM.
尽管采用了传统疗法和高剂量疗法，多发性骨髓瘤（MM）在很大程度上仍然无法治愈，因此迫切需要基于生物学的新型治疗方法。最近的研究表明，包括白细胞介素（IL）-6、胰岛素样生长因子（IGF）-1、血管内皮生长因子（VEGF）、肿瘤坏死因子（TNF）家族蛋白、Wnt和Notch家族成员在内的多种生长因子在MM发病机制中起重要作用，并介导肿瘤细胞在骨髓（BM）微环境中的增殖、耐药性和迁移。因此，靶向生长因子是MM中一种有前景的治疗策略。抑制生长因子信号级联的新型药物可以靶向MM细胞和BM微环境中的配体、受体和/或下游信号级联蛋白。这些新型药物与传统疗法联合使用，不仅可以增强细胞毒性，还可以避免耐药性，从而改善MM患者的预后。
