Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Table 3 Therapeutic targets, bone anabolic drugs and preclinical/clinical studies in the context of myeloma bone disease or other bone diseases

Drug	Mechanism of action	Signaling pathway	Cell target	Preclinical studies	Phase of clinical trials
BHQ880	Neutralizing anti-DKK1 antibody	Wnt	MSC, MMPC	[122,123,125]	II[126,127]
Romosozumab (AMG785)	Neutralizing anti-sclerostin antibody		MSC	[79,83]	II (postmenopausal osteoporosis)[129]
LiCl	GSK3β inhibitor		MSC, MMPC	[131]	NA
DAPT	γ-secretase inhibitor	Notch	MSC, MMPC	[110,142]	NA
GSI15			OC, MMPC	[139]
Bortezomib and second generation PIs	Proteasome inhibitor	UPR	MSC, OC, MMPC	[179,180,201]	Bortezomib and carfilzomib: Approved Oprozomib: I/II Ixazomib: III
RAP-011 (mouse) Sotatercept/ACE-011 (human)	Decoy receptor neutralizing activin A	BMP	MSC, OC, MMPC	[61,62]	II[153,154]
SB431542	TGFβ inhibitor		MSC	[150]	NA
Ki26894			MSC
MLN3897	CCR1 antagonists	CCL3	MSC, OC, MMPC	[58,160]	NA
CCX721 (mouse) CCX354-C (human)			OC, MMPC	[157]	II (rheumatoid arthritis)[161]

MSC: Mesenchymal stromal cell; MMPC: Multiple myeloma plasma cell; OC: Osteoclast; NA: Not applicable; DKK1: Dickkopf-1; GSK3β: Glycogen synthase kinase 3β; DAPT: N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; TGFβ: Transforming growth factor β; UPR: Unfolded protein response; BMP: Bone morphogenetic protein; CCR1: Chemokine (C-C Motif) receptor 1; CCL3/MIP1α: Macrophage inflammatory protein 1-α.