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. 2021 Apr 1;13(7):1668. doi: 10.3390/cancers13071668

Figure 1.

Figure 1

Deregulated signaling cascades and pathway-directed therapies in multiple myeloma. (a) Signaling pathways in multiple myeloma. In multiple myeloma, genetic abnormalities and bone marrow microenvironment-driven deregulations, such as increased levels of IL-6, IGF1, HGF, VEGF, CXCL12, TNFα, BAFF, APRIL, and CCL3 derived from stromal, bone, and immune cells result in the activation of multiple signaling pathways, most prominently including the RAS/RAF/MEK/ERK-, PI3K/AKT-, NFκB-, and STAT-pathway but also the WNT-, Hedgehog-, and TNFα-pathway. They trigger tumor cell proliferation, survival, drug resistance, migration, secretion of humoral factors but also promote immunoparesis, bone marrow angiogenesis, and bone disease. (b) Pathway-directed therapies. Abbreviations: Bone marrow (BM), cell adhesion-mediated drug resistance (CAMDR), interleukin-6 (IL-6), B-cell activating factor (BAFF), A proliferation inducing ligand (APRIL) vascular endothelial growth factor (VEGF), C-X-C motif chemokine 12 (CXCL12), Signal transducer and activator of transcription (STAT), nuclear factor kappa B (NFκB), phosphoinositide 3-kinase (PI3K), Janus kinase (JAK), Mouse double minute 2 homolog (Mdm2), CREB-regulated transcription coactivator 1 (TORC1), CREB-regulated transcription coactivator 1 (TORC2), protein kinase B (AKT), RAS-kinase (RAS), B-RAF-kinase (BRAF), C-RAF-kinase (cRAF), mitogen activated protein kinase (MAPK), mitogen activated protein kinase kinase (MEK), proviral insertion site of Moloney murine leukemia virus kinase (PIM), Activator protein-1 (AP-1).