Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Table 1

Details of selected trials with therapeutic Notch-targeting agents for lung cancer treatment.

Class	Mechanism	Drug	Target	Condition	Development phase	Trial status/ID
mAbs to Notch receptors or ligands (neutralizing antibody)	Interference with ligand-induced Notch subunit separation and Notch ligands	OMP21M18 +	DLL4 (Delta-like ligand 4)	Nonsquamous NSCLC	Ib	Active, not recruiting/NCT01189968
		OMP-59R5 + / or	Notch2/Notch3	Stage IV Small Cell Lung Cancer (SCLC)	Ib/II	Recruiting/NCT01859741
mAbs to Wnt signaling pathway (monoclonal antibody)	Blocking canonical WNT/β-catenin signaling through binding of five FZD receptor	OMP-18R5 +	Wnt cancer stem cell pathway	Recurrent or advanced NSCLC	Ib	Recruiting/NCT01957007
γ-Secretase inhibitor (GSI)	Inhibition of final Notch cleavage by γ-secretase	RO4929097	Notch1, Notch2, Notch3, Notch4, Notch ligands	Recurrent NSCLC Stage IIIB NSCLC Stage IV NSCLC	II	Terminated/NCT01193868
		RO4929097 + OSI-		Recurrent NSCLC Stage IV NSCLC	I	Terminated/NCT01193881
		BMS-906024		Advanced/metastatic squamous NSCLC	I	Ongoing/NCT01292655
		BMS-906024 + chemotherapy		Advanced/metastatic squamous NSCLC	Ib	Ongoing/NCT01653470
		BMS-906024 +		NSCLC	I	Synergistic antitumor activity of the Notch gamma secretase inhibitor BMS-906024 and paclitaxel in the treatment of lung adenocarcinoma. Abstract 2535, AA
γ-Secretase inhibitor (GSI)/VEGFR tyrosine kinase inhibitor	Inhibit of final Notch cleavage by γ-secretase and stop the growth of tumor cells by blocking some of the enzymes needed for cell growth	RO4929097 + AZD2171		Recurrent NSCLC Stage IIIA NSCLC Stage IIIB NSCLC Stage IV NSCLC	I	Completed/NCT01131234

agent: CP (carboplatin plus paclitaxel); EP (etoposide), CDDP (cisplatin), CBDCA (carboplatin); DTX (docetaxel); OSI-774 (Erlotinib); chemoregimens: PTX (paclitaxel), 5-FU plus irinotecan (FOLFIRI), or CP (carboplatin plus paclitaxel).
Each status of development phases results from https://www.clinicaltrials.gov/.