Table 2.

The most promising novel therapeutic options in ENKTL are summarized. The biological basis for targeting these pathways along with available clinical data are shown

Signaling pathway or therapeutic target	Biological basis for selection as a therapeutic target	Clinical data	References
JAK3	JAK3 mutations are frequent in ENKTL. JAK3 inhibition is shown to have potent anti-tumor activity in pre-clinical models	Clinical trials evaluating JAK inhibitors in ENKTL are in progress. (NCT02974647)	Sim et al. [19] Narisimagi et al. [24]
STAT-3	STAT3-mutant ENKTLs are sensitive to STAT3 inhibition in vitro.	Not available.	Sim et al. [19]
NF-κB	NF-κB upregulation is an important event in ENKTL pathogenesis.	Bortezomib is being evaluated in early phase clinical trials for ENKTL	Chen et al. [35] Tang et al. [36]
CD38	CD38 is upregulated in ENKTL. Daratumumab has good in vitro efficacy.	One case report documenting complete response in a relapsed refractory patient.	Mustafa et al. [153] Hari et al. [154]
PD-1	PD-L1 is upregulated in ENKTL.	Early clinical trials show potent single-agent activity of anti-PD-1 therapy in relapsed, refractory ENKTL.	Kwong et al. [11]