Table 1. Emerging therapies targeting novel aberrant pathways in Multiple Myeloma.
Abbreviations: BCL-2=B cell lymphoma-2, JAK-STAT=Janus kinase Signal Transducer and Activator of Transcription proteins, MEK=Mitogen activated protein kinase kinase, FGFR=fibroblast growth factor receptor, NF-KB=nuclear factor kappa light chain enhancer of activated B cells, mTOR=mammalian target of rapamycin, MM=multiple myeloma, NSD2=nuclear receptor binding SET domain2, BET=bromodomain and extra terminal, BRD=bromodomain, MYC=Myeloctomatosis (oncogene), HDAC=histone deacetylase
| Pathway | Drug Name | Mechanism of action | Clinical Trial |
|---|---|---|---|
| BCL-2 overexpression | |||
| venetoclax (ABT-199) | BCL-2 inhibitor | NCT01794520 | |
| JAK-STAT | |||
| ruxolitinib | JAK2 inhibitor | NCT00639002 | |
| SC99 | JAK2/STAT3 inhibitor | ||
| NF-KB | |||
| DANFIN | Proteasome inhibitor-inhibits NF-KB activation and signaling | ||
| Ras/Raf/Mek/Erk | |||
| selumetinib (AZD6244) | MEK 1/2 inhibitor -blocks the MEK immediately downstream of BRAF | NCT01085214 | |
| sorafenib | Multi kinase inhibitor-inhibits cell surface TKIs and downstream intracellular serine/threonine kinases | ||
| vemurafenib | BRAF inhibitor | NCT01524978 | |
| cobimetinib | BRAF inhibitor | NCT03312530 | |
| FGFR mutation | |||
| MFGR1877S | Anti-FGFR monoclonal antibody | ||
| dovitinib (TKI258) | Non selective FGFR inhibitor | NCT02465060 | |
| BGJ398 | Non selective FGFR inhibitor | ||
| AZD4547 | FGFR (1-3) inhibitor | ||
| Cyclin D | |||
| palbociclib | CDK4/6 inhibitor | ||
| PI3K/AKT/mTOR | |||
| clioquinol | Hydroxyquinoline, downregulates expression of mTOR, inducing autophagy in MM cells | NCT00963495 | |
| SC-06 | Disrupts mTOR signaling pathway by downregulating Raptor, a key component of mTORC1 signaling | ||
| BEZ235 | mTOR inhibitor | ||
| C98 | PI3K/AKT inhibitor | ||
| C96 | PI3K/AKT inhibitor | ||
| Epigenetic regulation | |||
| LEM06 | MMSET/NSD2 inhibitor (histone methyl transferase inhibitor) | ||
| JQ-1 | BET inhibitor | ||
| CPI-0601 | BET inhibitor | ||
| OTX015/MK8628 | BET inhibitor | NCT01713582 | |
| CPI-203 | BET inhibitor | ||
| CGI13250 | Suppresses MYC transcription by blocking BRD4 binding to MYC promoter | ||
| panobinostat | HDAC inhibitor |
NCT01651039 NCT01023308 |
|
| vorinostat | HDAC inhibitor | NCT00773838 | |
| romidepsin | HDAC inhibitor |
NCT00066638 NCT01755975 |
|
| ricolinostat | HDAC inhibitor | NCT01323751 |