Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches

Table 2 Therapeutic strategies targeting mechanical forces in the TME

Therapeutic Agent	Target	Experimental Model	Key Effects	Reference
β-APN	LOX	MDA-MB-231 cell	Inhibit LOX enzyme activity and protein expression, reduce the phosphorylation of paxillin at Tyr-31 and Tyr-118 mediated by the FAK/Src complex, and suppress collagen cross-linking.	[219]
magnolol	LOX	MDA-MB-231 cell		[219]
PAT-1251	LOX2	MDA-MB-231 cell	Inhibit CAF activation and reduce new blood vessel formation.	[223]
Cilengitide	Integrin	NSCLC A549 cell	Inhibit TGF-β1-induced expression of cancer cell migration markers, activation of Smad2/3, and invasion capability of NSCLC A549 cells.	[227]
Saridegib	Smoothened	KPC mice	Deplete tumor stroma, increase vascular density, and enhance tumor perfusion	[235]
PEGPH20	Hyaluronan	KPC mice	Degradation of HA in PDA tumor endothelial cells induced the formation of fenestrations and intercellular gaps, increasing macromolecular permeability.	[236]
Losartan	Angiotensin-II-receptor-1	E0771 tumor model in wild-type C57BL/6 mice	Reduce the expression of profibrotic signals TGF-β1, CCN2, and ET-1, and decrease the production of stromal collagen and hyaluronan.	[237]
Bevacizumab	Vascular endothelial growth factor	Patients with advanced rectal cancer	Reduce the interstitial fluid pressure and blood flow in the tumor.	[191]
Bediranib	VEGF receptor tyrosine kinase	glioblastoma patients	Inhibit vascular growth factors to control abnormal tumor vascular proliferation and improve tumor blood flow and oxygenation.	[243]

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