An Update on Novel Therapeutic Warfronts of Extracellular Vesicles (EVs) in Cancer Treatment: Where We Are Standing Right Now and Where to Go in the Future

Table 3

Several potential EV biomarkers found in different body fluids.

Cancer type	Body fluid	Biomarker	Method/technique	Clinical significance	Reference
Breast cancer	Plasma serum	Integrins	ELISA	Src activation and upregulation of proinflammatory S100 genes	[100]
		miR-9	qRT-PCR
		HER2, CD47, Del-1, miR-1246, miR-21	Microfluidic chip; Adaptive dynamic artificial polyligand targeting (ADAPT)	Upregulated, miR-1246 attacks CCNG2 and promotes drug resistance against cancer	[192]
		Glutathione S-transferase P1 (GSTP1), ubiquitin carboxyl terminal hydrolase-1 (UCH-L1), NANOG, NEUROD1, HER2, KDR, CD49d, CXCR4, CD44, miR-340-5p, miR-130a-3p, miR-93-5p, miR-17-5p	qRT-PCR; FCM; PCR array	Partial remission (PR)/complete remission (CR); Progression-free survival (PFS); Disease-free survival (DFS); Distant organ metastasis; Recurrence	[193]
		TRPC5	Confocal analysis, Western blot	Elevated levels show poor prognosis	[194]
		Survivin	ELISA	Elevated survivin-ΔEx3 splice variant, while differential expression of survivin-2B in BC patients	[195]
		Periostin	Nanoparticle tracking analysis	Higher levels in patients with lymph node metastasis	[196]
		miR-373	qRT-PCR	Controversial effect on BC	[197]
Glioblastoma	Cerebrospinal fluid (CSF); Serum	EGFRvIII	Western blot	Mutated EGFRvIII cause: increase mitogenic factor Akt, suppress apoptosis, downregulate Bcl-2	[198]
		PTRF/caveolin-1, miR-21	qRT-PCR	Elevation leads to recurrence	[181]
		DNM3, p65, p53	Microarray	Elevated levels in primary and recurrent GBC	[199]
Melanoma	Serum; Plasma	MDA-9, GRP78	Western blot	Elevation in metastasis	[200]
		miR-125b	Western blot	Melanoma patient PDS and OS patients showed high survival	[201]
		PD-1, CD28	qRT-PCR	Downregulation leads to MM progression	[202]
		MIA, S-100	Immunoaffinity capture	Interaction with ECM proteins: promote metastasis	[203]
		CD63, caveolin-1	In-house sandwich ELISA (Exotest)	Elevated levels in MP	[204]
Hepatocellular carcinoma (HCC)	Serum	TAK1	Microarray analysis	Upregulation	[205]
		miR-320a	qRT-PCR	Cancer suppression	[206]
		miR-122	qRT-PCR	Upregulate septin-9: taxol resistance	[207]
		miR-21, 211, 222, 224	qRT-PCR	Upregulation in cancer patients	[208]
		miR-718, 1246	qRT-PCR	Downregulation causes HCC progression, miR-718 targets EGR-3 and increases proliferation	[209]
Ovarian cancer	Plasma; Serum	miR-21, 141, 200a, 200c, 200b, 203, 205, 214, 222-3p	miRNA array	Suppress apoptosis through binding to APAF1, grant paclitaxel resistance. miR-21 targets Bcl-2, TPM1, PDCD4, maspin, and PTEN leading to tumor proliferation. miR-200 attacks ZEB1/2 leading to EM. miR-205 targets the HER2 pathway causing tumor suppression	[210]
		Phosphatidylserine	Nanoparticle tracking analysis	Elevated levels in cancer patients	[211]
		Claudin-4	Western blot	Upregulation in OC patients	[212]
Multiple myeloma	Serum	MSC-derived miR-15a, Let-7b, miR-18a	qRT-PCR array analysis	Suppressor of MM; Elevated levels in cancer patients	[213]
Colorectal cancer (CRC)	Serum	miR-9	qRT-PCR	Inhibits suppressive expression SOCS5, upregulate endothelial cell migration	[214]
		CRNDE-h, miR-19a-3p, 21-5p, 425-5p, 17-92a	ExoScreen	Upregulation in cancer patients	[215]
		miR-4772-3p	qRT-PCR	Lower level causes cancer recurrence	[216]
		let-7a, miR150, 1246, 1229, 223, 21, 23a	qRT-PCR	let-7a binds KRAS and inhibits cancer, miR-21 downregulates p53	[217]
Prostate cancer	Serum; Urine; Plasma	LncRNA-p21, miR-21, 375; miR-1290	qRT-PCR	Elevation in prostate cancer patients	[218]
		PSA, PSMA, P-glycoprotein	qRT-PCR	Elevation causes castration-resident prostate cancer; Elevation in docetaxel-resistant patients	[219]
		miR-1246	Western blot	Overexpression leads to positive metastasis	[220]
		TM256, LAMTOR1, VATL, ADIRF, survivin	qRT-PCR; ELISA	VATL increases metastasis, LAMTOR1 regulates mTOR signaling	[221]
Pancreatic cancer	Serum	Glypican-1; miR-1246, 4644, 3976, 4306	GFP; qRT-PCR	Increased levels in pancreatic cancer patient’s upregulation in 83% of pancreatic cancer patients	[222]
		CD44, V6, Tspan8, EpCAM, CD104	ELISA	CD44v6 target MET and VEFGR-2 pathways to promote metastasis	[223]
Non-small-cell lung cancer (NSCLC)	Plasma	miR-302c, 302a, 126	Western blot	Elevation in cancer patients	[224]
	Bronchoalveolar lavage	EML4-ALK	Electron microscopy
		miR 181-5p, 30a-3p, 361-5p, 15b-5p, 320b, 30e-3p	Nanoparticle tracking analysis
		EpCAM, NY-ESO-1, Alix, PLAP, miR-24	miRNA-seq	EFGR mutation leads to metastasis, miR-24 targets Jab1/CSN5 to promote tumorigenesis	[225]
Acute myeloid leukemia (AML)	Plasma	CD34	Immunoaffinity capture	Elevated CD34+ exosomes in AML patients	[226]
Cervical cancer	Cervicovaginal lavage specimens	miR-21, 146a	qRT-PCR	Elevation in HPV+ patients	[227]
		Survivin	qRT-PCR	Suppress genotoxic-induced stress apoptosis and enhance proliferation	[228]
Bladder cancer	Serum; Urine	Lnc-UCA1	qRT-PCR	Elevated expression in BC patients	[229]
		EDIL-3	Western blot	Tumor progression via activation of EFGR	[230]