Table 1.

Notch targeted therapy in PC.

Class	Drug	Target	Study type	Results	Reference
GSI	R04929097	γ-secretase	Clinical trial	>4 months stable disease	Yuan X Cancer Letters, 2015 [97]
	PF-03084014		Pre-clinical	Reduces PCSC, xenograft growth	Yabuuchi S Cancer Letters, 2013 [98]
	MRK-003		Pre-clinical	Induces apoptosis and tumor necrosis	Mizuma M Carcinogenesis, 2013 [101]
	MK-0752		Clinical trial	68% of patients achieved stable disease	Cook N Br J Cancer, 2018 [102]
GSI+JAK2 inhibitor	GSI IX + AG-490	γ-secretase +JAK2	Pre-clinical	Suppresses the conversion of acinar-ductal metaplasia to PC	Palagani V Carcinogenesis, 2013 [99]
Monoclonal antibody	Tarexumab	Notch2, Notch3	Pre-clinical	Reduces tumor xenograft growth	Knudsen ES Gastroenterology, 2016 [103]
			Clinical trial (+Gemcitabine, nab-Paclitaxel)	5-6 months PFS11.6 months OS
	Demcizumab	DLL4	Clinical trial (+Gemcitabine,Nab-Paclitaxel)	No difference to chemotherapy	Gracian AC Annals of Oncology, 2017 [104]
Other treatments	Quinomycin	Antibiotic	Pre-clinical	Reduces PCSC and tumor growth	Ponnurangam S Oncotarget, 2016 [105]
	Genistein	Isoflavone	Pre-clinical	Reduces apoptosis through upregulation of miR-34a	Xia J Curr Drug Targets, 2012 [106]
	Fendiline	ADAM10	Pre-clinical	Reduces cell proliferation, migration and PCSC	Woods N Oncotarget, 2015 [107]
	IMR-1	Mastermind Recruitment-1	Pre-clinical	Disrupts the formation of NICD1-MAML1-RBPJ activation complex	Astudillo L Cancer Research, 2016 [108]
	IONP-LPrA2	OB-R	Pre-clinical	Reduces PC xenograft growth and re-sensitizes PC cells to chemotherapy	Harbuzariu A Oncotarget, 2017 and 2018 [2,37]

PFS: progression free survival; OS: overall survival; OB-R: leptin receptor; GSI: γ-secretase inhibitor.