Various Signaling Pathways in Multiple Myeloma Cells and Effects of Treatment on These Pathways

被引:45
作者
Dehghanifard, Ali [1 ]
Kaviani, Saeid [1 ]
Abroun, Saeid [1 ]
Mehdizadeh, Mahshad [2 ]
Saiedi, Sajedeh [3 ]
Maali, Amirhosein [4 ]
Ghaffari, Sasan [5 ]
Azad, Mehdi [4 ]
机构
[1] Tarbiat Modares Univ, Dept Hematol, Fac Med Sci, Tehran, Iran
[2] Islamic Azad Univ, Tehran Med Sci Branch, Tehran, Iran
[3] Ahvaz Jundishapur Univ Med Sci, Hlth Res Inst, Res Ctr Thalassemia & Hemoglobinopathy, Ahvaz, Iran
[4] Qazvin Univ Med Sci, Fac Allied Med, Dept Med Lab Sci, Qazvin 3419759811, Iran
[5] Univ Tehran Med Sci, Fac Allied Med, Dept Hematol, Tehran, Iran
关键词
Bortezomib; CAM-DR; Dexamethasone; IL-6; MEDIATED DRUG-RESISTANCE; NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW; PROTEASOME INHIBITORS; IN-VITRO; CAM-DR; TARGETED THERAPY; APOPTOSIS; EXPRESSION;
D O I
10.1016/j.clml.2018.03.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma ( MM) results from malignancy in plasma cells and occurs at ages > 50 years. MM is the second most common hematologic malignancy after non-Hodgkin lymphoma, which constitutes 1% of all malignancies. Despite the great advances in the discovery of useful drugs for this disease such as dexamethasone and bortezomib, it is still an incurable malignancy owing to the development of drug resistance. The tumor cells develop resistance to apoptosis, resulting in greater cell survival, and, ultimately, develop drug resistance by changing the various signaling pathways involved in cell proliferation, survival, differentiation, and apoptosis. We have reviewed the different signaling pathways in MM cells. We reached the conclusion that the most important factor in the drug resistance in MM patients is caused by the bone marrow microenvironment with production of adhesion molecules and cytokines. Binding of tumor cells to stromal cells prompts cytokine production of stromal cells and launches various signaling pathways such as Janus-activated kinase/signal transduction and activator of transcription, Ras/Raf/MEK/mitogen-activated protein kinase, phosphatidyl inositol 3-kinase/AKT, and NF-KB, which ultimately lead to the high survival rate and drug resistance in tumor cells. Thus, combining various drugs such as bortezomib, dexamethasone, lenalidomide, and melphalan with compounds that are not common, including CTY387, LLL-12, OPB31121, CNTO328, OSI-906, FTY720, triptolide, and AV-65, could be one of the most effective treatments for these patients.
引用
收藏
页码:311 / 320
页数:10
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