Table Info

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]

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

Declarations

Author contributions

SO performed data analyses and the writing of the paper. JM supervised the writing of the paper.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by grants from INCa (Institut National du Cancer) PLBIO18-362 PIT-MM and PLBIO19-098 INCA_13832FATidique, ANR (the French National Research Agency) under the “Investissements d’avenir” program with the reference ANR-16-IDEX-0006, ANR (TIE-Skip; 2017-CE15-0024-01), ANR-18-CE15-0010-01 PLASMADIFF-3D, SIRIC Montpellier Cancer (INCa_Inserm_DGOS_12553), Labex EpiGenMed and Institut Universitaire de France. The funders had no role in analysis, decision to publish, or preparation of the manuscript.

Copyright

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