de la Puente Pilar, Muz Barbara, Azab Feda, Luderer Micah, Azab Abdel Kareem
Cancer Biology Division, Department of Radiation Oncology, Washington University in Saint Louis School of Medicine, 4511 Forest Park Avenue, Room 3103, Saint Louis, MO 63108, USA.
Leuk Res Treatment. 2014;2014:976567. doi: 10.1155/2014/976567. Epub 2014 Apr 16.
Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients will eventually relapse or become refractory to the treatments. Although the treatments have improved, the major problem in MM is the resistance to therapy. Novel agents are currently in development for the treatment of relapsed/refractory MM, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, cell signaling targeted therapies, and strategies targeting the tumor microenvironment. We have previously reviewed in detail the contemporary immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies therapies for MM. Therefore, in this review, we focused on the role of molecular targeted therapies in the treatment of relapsed/refractory multiple myeloma, including cell signaling targeted therapies (HDAC, PI3K/AKT/mTOR, p38 MAPK, Hsp90, Wnt, Notch, Hedgehog, and cell cycle) and strategies targeting the tumor microenvironment (hypoxia, angiogenesis, integrins, CD44, CXCR4, and selectins). Although these novel agents have improved the therapeutic outcomes for MM patients, further development of new therapeutic agents is warranted.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，由于大多数患者最终会复发或对治疗产生耐药，因此仍然无法治愈。尽管治疗方法有所改进，但MM的主要问题是对治疗的耐药性。目前正在研发用于治疗复发/难治性MM的新型药物，包括免疫调节药物、蛋白酶体抑制剂、单克隆抗体、细胞信号靶向疗法以及针对肿瘤微环境的策略。我们之前已经详细综述了MM的当代免疫调节药物、蛋白酶体抑制剂和单克隆抗体疗法。因此，在本综述中，我们重点关注分子靶向疗法在复发/难治性多发性骨髓瘤治疗中的作用，包括细胞信号靶向疗法（组蛋白去乙酰化酶、磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白、p38丝裂原活化蛋白激酶、热休克蛋白90、Wnt、Notch、Hedgehog和细胞周期）以及针对肿瘤微环境的策略（缺氧、血管生成、整合素、CD44、CXC趋化因子受体4和选择素）。尽管这些新型药物改善了MM患者的治疗效果，但仍有必要进一步开发新的治疗药物。
