Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies

Table 2 Recent experimental studies of targeted therapy for pancreatic cancer

Targeted therapeutics	Ref.	Cell lines (cell type)	Main results
Multikinase inhibitors
Foretinib	Chen et al[32]	Panc-1(P)	Foretinib inhibited tumor growth, angiogenesis and lymphangiogenesis in xenograft animals, by inhibiting c-MET but VEGFR-2, VEGFR-3, and TIE-2 signaling
SKLB261	Pan et al[80]	BxPC-3 (P),	Application of SKLB261 resulted in more potent antitumor activities than dasatinib, gemcitabine, or erlotinib in pancreatic cancer xenografts
		Panc-1 (P),
		AsPC-1 (S), HPAC (P)
Nintedanib	Awasthi et al[81]	AsPC-1 (S),	A triple angiokinase inhibitor, nintedanib inhibited growth of pancreatic cancer cell lines, with gemcitabine enhancing inhibitory effects
		BxPC-3 (P),
		Panc-1 (P),
		MIA-PaCa-2 (P),
Dual inhibition
Lapatinib and trametinib	Lindberg et al[101]	MAD 08-608, 08-738, 09-366 (P)	Dual anti-EGFR and anti-HER2 therapy significantly enhanced the growth inhibitory effects of the MEK1/2 inhibitor trametinib
ZSTK474 and RO5126766	Van Dort et al[99]	Panc-1 (P)	PI3K inhibitor and the Raf/MEK inhibitor RO5126766 resulted in high in vitro inhibition of both PI3Kand MEK1 also decreased cellular viability in pancreatic cancer cell line
NVP-AEW541 and lapatinib	Urtasun et al[42]	NP-9, -18, -29 (P)	Combined treatment with the IGF-IR and EGFR/Her-2 inhibitors synergistically inhibited pancreatic cancer cell growth which is associated with abolishment of Akt, Efk, and IRS-1 activity
		CP15T, ,15A (p)
Novel pathways
PX-478 (HIF-a)	Zhao et al[84]	CFPAC-1 (S), BxPC-3 (P),	Combined treatment with gemcitabine/PX-478 significantly enhanced the anti-tumor effect which is associated with immunogenic cell death
		Panc-1 (P),
		MIA-PaCa-2 (P)
SB216763(GSK-3b)	Marchand et al[86]	Panc-1 (P),	Inhibition of GSK-3βn induced apoptosis by mechanism involving JNK-cJUN activation
		MIA-PaCa-2 (P), BxPC-3 (P)
Micro RNA
miR-142-3p	MacKenzie et al[95]	MIA-PaCa-2 (P), Capan-1(S),	A unique HSP70 inhibiting compounds, miR-142-3p regulate triptolide-induced inhibition of pancreatic cancer growth
		HEK-293 (P),
		S2-013 (P)
miR-146a	Li et al[96]	AsPC-1 (s),	miR-146a takes significant roles in pancreatic cancer invasion and metastasis but lower expressed in pancreatic cancer compared with normal pancreatic tissue
		Panc-1 (P)
miR-494	Li et al[97]	Colo357 (s),	miR-494, identified to affect levels of FOXM1 in pancreatic cancer cell lines and act as a negative regulator of this transcriptional activator, blocked nuclear translocation β-catenin
		Panc-1 (P)

VEGF: Vascular endothelial growth factor; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2; MEK: Mitogen-activated ERK kinase; PI3K: Phosphatidylinositol-3 kinase; IGF-1R: Insulin-like growth factor 1 receptor; FGFR: Fibroblast growth factor receptor; HSP: Heat shock protein; FOXM1: Forkhead box M1; P: Primary; S: Secondary.