Review Article

Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

Table 2

Therapeutic agents with reported activity on OS-CSCs subpopulations or related properties.

Therapeutic agentProposed mechanisms of actionEffect on CSC/CSC propertiesReference

Parthenolide NF-κB inhibition/oxidative stress inductionSensitizes to ionizing radiation reducing the viability of CD133+ CSCs[31]
BRM270 NF-κB/CDK6/IL6 downregulationInduces programmed cell death[32]
BYL719PI3K inhibitionInduces cell cycle arrest and inhibits migration[33]
LY294002PI3K inhibitionInduces cell cycle arrest and apoptosis in OS-sarcospheres[34]
SB431542TGF-β inhibitionReduces self-renewal and differentiation and increases chemosensitivity of OS-sarcospheres[35]
miR-382 expressionYB-1 inhibitionDecreases OS-CSCs, reduces metastatic potential, and inhibits tumor formation from CD133+ OS cells[36]
miR-29b-1 expressionReduces sarcosphere formation and induces chemosensitization of OS cells[37]
miR-133a inhibitionReduces cell invasion of CD133+ OS cells and suppresses metastasis in combination with chemotherapy[38]
lncRNA HIF2PUTHIF-2αReduces CD133+ cells and impairs sphere-forming in OS cells[39]
MetforminAMPK/mTOR signaling alterationReduces sphere-forming ability and sensitizes OS cells to chemotherapeutic agents [40, 41]
Bufalin miR-148a/DNMT1/CDKN1BInhibits differentiation and proliferation of OS-sarcospheres [42, 43]
SalinomycinWNT signaling downregulationReduces sphere-formation and tumor-initiation ability of OS cells and sensitizes them to chemotherapeutic drugs[44]
Salinomycin-loaded nanoparticlesWhen combined with CD133 aptamers selectively targets OS-CD133+ cells[45]
Diallyl trisulfideUpregulation of tumor-suppressive miRNAs/inhibition of NOTCH1 signaling/downregulation of ABCB1Prevents invasion, angiogenesis, and drug resistance in OS cells and in combination with methotrexate reduces OS-CD133+ cells [46, 47]
MC1742/MC2625Histone deacetylase inhibitionInduces apoptosis and promotes differentiation of sarcoma CSCs[48]
VorinostatHistone deacetylase inhibitionReduces metastatic potential of OS cells[49]
Anti-CD47 antibodyIncreased macrophage phagocytosisInhibits invasion and metastasis of OS cells[50]

CDK6: cyclin-dependent kinase 6; IL6: interleukin 6; TGF-β: transforming growth factor β; YB-1: Y box-binding protein 1; HIF-2α: hypoxia inducible factors 2α; AMPK: AMP-activated protein kinase; mTOR: mechanistic target of rapamycin; DNMT1: DNA (cytosine-5-)-methyltransferase 1; CDKN1B: cyclin-dependent kinase inhibitor 1B; WNT: wingless-type MMTV integration site family; ABCB1: ATP-binding cassette subfamily B member 1.