Table 2.

Example of therapeutic modalities by exploiting micropinocytosis in cancers

Therapeutic modalities	drugs	Mechanism	Type of cancer	Reference
chemotherapy
NHE inhibitor	EIPA	impact on submembranous alkaline pH	RAS-driven cancer	[1,42,73]
v-ATPase inhibitor	bafilomycin A1	impact on lysosomal acidic pH	RAS-driven cancer	[74]
EGFR inhibitor	gefitinib	inhibit the macropinocytosis pathway	NSCLC	[75]
Galectin-3 inhibitor	GCS-100	inhibit the macropinocytosis pathway	Lung cancer or pancreatic cancer	[28]
DOCK1 inhibitor	TBOPP	repress DOCK1-mediated macropinocytosis	RAS-driven cancer	[76]
actin inhibitors	blebbstatin	inhibit actin polymerization	RAS-driven cancer	[77]
	cytochalasin D	inhibit actin polymerization	RAS-driven cancer	[78]
PI3K inhibitors	Wortmannin, LY294002	inhibit PI3K signaling pathway	RAS-driven cancer	[79]
Pak1 inhibitor	IPA-3	impact on actin polymerization	RAS-driven and WNT-driven cancer	[48]
lysosomal inhibitor	PPT1	suppress lysosomal activity	pancreatic cancer or colorectal cancer	[80,81]
mTOR inhibitors	torin1 and AZD2014	suppress proteins scavenging	RAS-driven cancer	[2,23]
AMPK activator	sepantronium bromide	block mTORC1	prostate cancer	[64]
CK2 inhibitor	silmitasertib	massive macropinocytosis	colorectal cancer	[39]
inducers	MOMIPP	massive macropinocytosis	GBM	[55]
	bacoside A	massive macropinocytosis	GBM	[56]
	NGF	massive macropinocytosis	medulloblastoma	[58]
	METH	massive macropinocytosis	neuroblastoma	[59]
anti-cancer agents conjugation	albumin-conjugated DOX	increase anti-cancer drugs to cancer cells through micropinocytosis	PDAC	[82]
	nab-paclitaxel with gemcitabine	increase anti-cancer drugs to cancer cells through micropinocytosis	PDAC	[83]
	T-UPSM	pH-triggered rapid drug release in lysosomes	PDAC	[84]
	TBM1 with 5-FU	induce macropinocytosis and increase 5-FU transport into cancer cells	colorectal cancer	[85]
	MOMIPP with temozolomide	massive micropinocytosis and increase uptake of temozolomide	GBM	[49]
Immunotherapy
mAbs	bevacizumab	target intracellular VEGF	NSCLC	[89]
	ScFv	target EGFR	pancreatic cancer	[93]
vaccines	BCG	using macropinocytosis	bladder cancer	[46]
	MTBVAC	using macropinocytosis	bladder cancer	[94]
	ApoE3-incorporated biomimetic nanoparticle	target macropinocytosis pathway	metastatic cancer	[95]
Nucleic acid therapy
nucleic acid drugs	TCTP ASOs	decreased expression of TCTP	prostate cancer	[97]
	TFEB siRNA	suppress TFEB	KRAS-mutant cancer	[101]
	ATF5 siRNA	inhibit cancer cell growth	GBM	[53]
	KRASG12D siRNA	decreased expression of KRASG12D	pancreatic cancer	[106]