HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma

Table 1

Novel strategies targeting HMGB1 in malignant mesothelioma.

Types	Substances	Biological effects on HMGB1	Cell models	Animal models	References
Polypeptides	Recombinant HMG Box-A	Recombinant HMG Box-A inhibits HMGB1 activity with more efficient HMGB1 targeting.	Phi cells	MM xenograft mouse model (injected with the human MM cell line REN)	[58]
			Primary HM cells	—	[45]
			REN cells, PPM-Mill cells, PPM-Phi cells	—	[44]
	Anti-HMGB1 neutralizing monoclonal antibody	An anti-HMGB1 neutralizing monoclonal antibody inhibits HMGB1 and the MM malignant phenotype.	REN cells, primary HM cells	SCID mice with human MM xenografts	[44]
Chemical pharmaceuticals	EP	EP affects the localization and secretion of HMGB1 in MM cells.; EP decreases serum HMGB1 levels in MM xenografts.	REN cells, HP3 cells	Orthotopic MM xenograft mouse model	[81]
	Aspirin and its metabolite, salicylic acid	Aspirin and its metabolite salicylic acid reduce the serum level of HMGB1 and suppress the secretion of HMGB1 by MM cells.	REN, HMESO, PPM-MILL, and Phi cells (primary MM cells)	Xenograft SCID mouse model (injected with the human MM cell line REN)	[58]
Plant extracts	Flaxseed lignans	Flaxseed lignans reduce HMGB1 gene expression and secretion in the blood.	—	MM-prone Nf2^+/mu mouse model	[90]

MM: malignant mesothelioma; HMG: high-mobility group; HMGB1: high-mobility group box 1 protein; HM cells: human mesothelial cells; SCID: severe combined immunodeficiency; BBIs: bromodomain inhibitors; PARP: poly (ADP-ribose) polymerase; EP: ethyl pyruvate.