Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect

Siak, Pui Yan; Heng, Win Sen; Teoh, Sharon Siew Hoon; Lwin, Yu Yu; Cheah, Shiau-Chuen

doi:10.1186/s12967-023-04673-8

Journal of Translational Medicine

Table 4 Signalling molecules targeted for therapeutic exploitation

From: Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect

Signalling pathway	Target	Oncogenic role	Potential therapeutic approach	Source
PI3K/Akt/mTOR	PI3K	NPC progression, CSC properties metastasis, radioresistance, cisplatin resistance and cytoskeleton dynamic	Inhibit PI3K by 2–4-morpholinyl-8-phenlchromone, omipalisib, gedatolisib, euscaphic acid or FOXO1	[36, 38, 117, 118]
	FGF2	Proliferation, migration, and invasion	Inhibited by miR-16	[119]
	Flot-2	Metastasis and cell proliferation	Silencing Flot-2	[120]
	DNMT1	Methylated miR152, downregulation of PTEN, activating Akt, inhibiting the miR-142-3p/Zinc-finger E-box binding homeobox 2 (ZEB2) axis (Invasion, migration, EMT and metastasis)	Downregulation	[121]
	SREBP1	Lipid synthesis promote cell proliferation and invasion	Downregulation	[122]
	EpCAM	CSC, metastasis	Downregulate by MK2206 and rapamycin	[123]
	HIF-1α	VM formation	Downregulation	[124]
	COL1A1	Radioresistance	Downregulating by MiR-29a	[125]
	RBM3	Radioresistance	Downregulation RBM3	[81]
	p85	Radioresistance and tumourigenesis	Interacting with leucine zipper tumor suppressor 2 (LZTS2)	[126]
	MK2	EMT, cisplatin resistance	downregulating by miR-296-3p	[127]
	VPS33B	Proliferation and chemoresistance	Upregulated by disrupting interaction with NESG1	[128]
	Cyclin D1(CCND1)	EMT	Downregulating miR-374a	[57]
	MDK	Angiogenesis	Downregulating of by MiR-9	[129]
TP53	MDM2	Chemoresistance	Competitive binding with Nutlin-3 and Idasanutlin	[130, 131]
	COX-2	Chemoresistance	Downregulation	[132]
	FOXO1	Chemoresistance, CSC and EMT	Upregulated by CB	[133]
	miR-125a and b	Anti-apoptosis	Downregulation	[134]
NF-κB	miR-203	EMT and metastasis	Upregulated by aspirin	[135]
	Pim 1	Cell proliferation	Suppressed by quercetagetin	[136]
	IKK	Anti-apoptosis	Downregulate by flavonoid glycoside vitexin	[137]
	VEGF	Angiogenesis	Suppressed by andrographolide	[138]
	ICAM	Apoptosis, cell proliferation
	MMP-9	Invasion and metastasis
	IκBα	Apoptosis and cell proliferation	Suppressed by simvastatin	[139]
	BST2	Chemoresistance	Downregulation	[140]
	SIRT6	Metastasis and anti-apoptosis	Upregulation	[141]
	NEAT1	Cell proliferation and anti-apoptosis	Knockout	[142]
	DLC-1	EMT	Upregulation	[143]
NF-κB	RERG	Angiogenesis cytokines, colony formation, invasion and migration	Demethylation	[144]
NF-κB	NF-κB p65	Cancer progression	Inhibited by EGCG	[145]
MAPK/ERK/JNK	Amyloid β precursor	Migration, invasion and EMT	Knockdown	[146]
	PAK1	Apoptosis	Inhibited by IVM	[147]
	MAP2K6	ROS and apoptosis	Inhibited by HI-TOPK-032	[148]
	MNK1	Apoptosis	Inhibited by compound 12dj	[149]
	MET	Cell proliferation and radioresistance	Inhibited by PHA-665752	[150]
	BLU	Cell cycle and apoptosis	Upregulation	[151]
	miR-124	TGF-β-induced migration, invasion and cell proliferation	Upregulation	[152]
	miR-483-5p	Colony formation, radioresistance and DNA damage	Downregulation	[153]
	CTAR1	Malignant transformation and cell survival	Inhibition	[154]
	PIN 1	Cell proliferation	Inhibited by juglone	[155]
JAK/STAT	STAT	Angiogenesis, migration, EMT, anti-apoptosis, cell proliferation and metastasis	Directly inhibited by ovatodiolide	[156]
	RKIP	Migration, invasion, metastasis and EMT	Upregulation	[157]
	miR-29a	Cell proliferation, anti-apoptosis and drug resistance (taxol)	Upregulation	[158]
	miR124-3p	Cell proliferation and anti-apoptosis	Upregulated by sulforaphane or knockout of UCA1 gene	[159, 160]
Wnt/β-catenin	CBP	CSC	Inhibited by foscenvivint	[161]
	β-catenin	CSC and radioresistance	Inhibited by binding of Chibby (Cby) to C-terminal of β-catenin • Inhibited it nuclear translocation by 14-3-3 adaptor proteins • Upregulation of miR-34c	[162, 163]
	Capn4	Proliferation and invasion	Inhibited by upregulation of miR-124	[164]
	LHX2	Radioresistance	Inhibited by upregulation of miR-506	[165]
	FOXO3a	Radioresistance	Upregulation	[166]
	Lgr5	Chemoresistance and EMT	Downregulation	[167]

Akt serine/threonine kinase 2, BLU zinc finger, MYNDtype containing 10, BST2 bone marrow stromal cell antigen 2, Capn4 calpain small subunit 1, CBP CREB binding protein, COL1A collagen type I alpha 1 chain, COX-2 cyclooxygenase-2, CSC cancer stem cell, CTAR1 carboxy-terminal activating region 1, DLC-1 deleted in liver cancer-1, D1(CCND1) cyclin D1, EGCG epigallocatechin-3-gallate, EMT mesenchymal transition, EpCAM epithelial cell adhesion molecule, FGF2 fibroblast growth factor 2, Flot-2 flotillin 2, FOXO1 forkhead box protein O1, FOXO3a forkhead box O3a, HIF-1α hypoxia-inducible factor 1-alpha, HI-TOPK-032 T-LAK-cell-originated protein kinase (TOPK) inhibitor, ICAM intercellular adhesion molecule 1, IKK IκB kinase, IκBα nuclear factor-kappa B inhibitor alpha, IVM ivermectin, Lgr5 G protein-coupled receptor 5, LHX2 LIM homeobox 2, MAP2K6 mitogen-activated protein kinase 6, MDK midkine, MDM2 murine double minute 2, MET mesenchymal epithelial transition, MK2 mitogen-activated protein kinase-activated protein kinase 2, MMP-9 matrix metalloproteinase, MNK1 mitogen activated protein kinase interacting kinases, mTOR mammalian target of rapamycin, NEAT1 nuclear enriched abundant transcript 1, NESG1 nasopharyngeal epithelium specific protein 1, NF-κB p65 nuclear factor kappa-light-chain-enhancer of activated B cells p65, NPC nasopharyngeal carcinoma, PAK1 P21 (RAC1) activated kinase 1, Pim 1 moloney murine leukemia virus-1, PIN 1 peptidyl-prolyl cis–trans isomerase NIMA-interacting 1, PI3K phosphoinositide 3-kinase, RBM3 RNA binding motif protein 3, RERG ras-like estrogen-regulated growth inhibitor, RKIP Raf kinase inhibitory protein, SIRT6 Sirtuin 6, STAT janus kinase, UCA1 urothelial cancer associated 1, VEGF vascular endothelial growth factor, VM vasculogenic mimicry, VPS33B vacuolar protein sorting 33B

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ISSN: 1479-5876

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