Exploration of Targeted Anti-tumor Therapy

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From: Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma

Table 1

Agents approved for MM treatment

Drug	Type	Target	Effect	Resistance
Melphalan Melflufen Cyclophosphamide	Alkylating agents	DNA	DNA damage Impairment of DNA replication and transcription	Misregulation/mutation of DDR pathways [25–31] Increased antioxidant defenses [32] Import/export alteration [33] miRNA misregulation [34]
Bortezomib Calfilzomib Ixazomib	PI	PSMB5 (26S proteasome)	Cytotoxicity by accumulation of aberrant proteins	BM microenvironment Upregulation of aggresomal protein degradation pathways Increased autophagy Proteasome subunit mutations Cell cycle misregulation [19, 20, 35, 36]
Thalidomide Lenalidomide Pomalidomide	IMiDs	CRBN	Immune activation Impaired angiogenesis Impaired proliferation of tumor cells Apoptosis induction	Low CRBN expression or mutation of its downstream targets [37–39]
Dexamethasone Prednisolone Methylprednisolone	Corticosteroids	GC receptors	Gene expression regulation Anti-inflammatory Immunosuppressive	Excess of IL-6 Defects on GC receptors FGFR3 overexpression [40–42]
Doxorubicin Pegilated liposomal doxorubicine (PDL)	Anthracyclines	DNA-Topo II	Impairment of DNA replication and transcription DSBs accumulation	DNA-Topo II mutations or misregulation [43–45] Efflux pumps overexpression [46]
Panobinostat	Histone deacetylase inhibitors	Histones	G1/S arrest Apoptosis Activation of tumor suppressor genes	Increased CXCR4, mTOR pathway activation, p21 up-regulation [47]
Daratumumab (DARA) Elotuzumab	Monoclonal Abs	CD38 CD319/ SLAMF7/CS1	ADCC, ADCP, CDC, immunomodulatory effects ADCC, NK-cell activation	Downregulation of the target Deregulation of ADCC, ADCP, CDC Stromal cell production of anti-apoptotic proteins PD1 and PD-L1 [48, 49]
Selinexor	Nuclear export inhibitors	XPO1	Nuclear export blockade Reduction of DDR proteins	(In vitro) alterations in signaling pathways downstream of XPO1 [50]

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ADCC: antibody-dependent cell-mediated cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; CDC: complement-dependent cytotoxicity