Exploration of Targeted Anti-tumor Therapy

Table 2. Selected therapeutic targets on AML niche

Mechanism	Targets	Cognate ligand in BM niche	BM niche	Drug	Clinical trials reference
Adhesion of leukemic stem cell to bone marrow niche	CD44	Hyaluronan, osteopontin	Endosteal niche	Polymeric nanoparticle-mediated silencing of CD44	N/R
	Selectin E	Selectin E ligand	Vascular niche	Uproleselan	[108, 109]
	VLA4	VCAM1	Vascular niche	AS101	N/R
CXCL12/CXCR4 axis	-	CXCR4	Vascular niche	Ulocuplumab	[108, 109]
				Plerixafor	[119, 120]
				CXCR4 antagonist LY2510924	[121]
Angiogenesis	-	VEGF	Vascular niche	Aflibercept	N/R
		VEGF	Vascular niche	Bevacizumab	[136]
		Angiopoietins	Vascular niche	Trebananib	[139]
Bone remodeling signaling pathway	-	Proteasome inhibitors	Vascular niche	Bortezomib	[143]
				Carfilzomib	[144]
				Ixazomib	[145]
		Receptor tyrosine kinase inhibitors	Vascular niche	Cabozantinib	[146]
Bone marrow adipose tissue remodeling	-	FAO inhibitors	Vascular niche	Avocatin B	N/R
Tumor immune evasion	-	PD1 inhibitor	-	Nivolumab	[170]
		PD1 inhibitor	-	Pembrolizumab	[171, 172]
		Anti-CTLA4	-	Ipilimumab	[167]

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-: no data. N/R: no reference; VLA4: very late antigen 4; VCAM1: vascular adhesion molecule 1; VEGF: vascular endothelial growth factor; FAO: fatty acid β-oxidation; PD1: programmed death 1; CTLA4: cytotoxic T-lymphocyte associated protein 4

Declarations

Author contributions

SK: Conceptualization, Writing—original draft, Writing—review & editing. MES and AEG: Data collection. GV: Funding acquisition. PPP: Supervision.

Conflicts of interest

Pier Paolo Piccaluga is the Editorial Board Member of Exploration of Targeted Anti-tumor Therapy and Guest Editor of Mechanisms of Targeted Therapy Resistance and Reversal Strategies, but he had no involvement in the journal review process of this manuscript. The other authors declare that there is no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

The work reported in this publication was funded by the Italian Ministry of Health [RC-2023-2778976, PRIN 2022NXK38S, and FIRB Futura 2011 RBFR12D1CB]. Giuseppe Visani received the support of AIL Pesaro Onlus. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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