Table 1.

This table describes the genes implicated in the pathogenesis of NKTL and the potential therapeutic targets

Gene	Therapeutic target	Comments
JAK3	Tofacitinib	First in class JAK 3 inhibitor. Single-agent JAK3 inhibition did not result in CR in NKTL cell lines [28]. Combination strategies may need to be explored
STAT3	AZD9150—antisense oligonucleotide inhibitor [30]	AZD9150 demonstrated promising activity in preclinical and clinical studies in lymphoma. Given that STAT3 activation leads to high PDL1 expression, combination of STAT3 and PD1/PDL1 inhibitors may be explored [19]
EZH2	DZNEP [43]	Non-specific EZH2 inhibitor that had significant toxicities in animal models
	Tazemetostat [50]	Phase 2 study shows promising activity in follicular lymphoma, especially in EZH2 mutated patients
	SHR2554	Selective small molecule inhibitor of the EZH2 histone-lysine methyltransferase ongoing phase 1 study in refractory lymphomas (NCT03603951)
	EPZ005687 [51]	Reduces H3K27 methylation in various lymphoma cell lines
	GSK126 [52]	Competitive small molecule inhibitor of S-adenosylmethionine. Has been tested in Diffuse large B cell lymphoma (DLBCL) and myeloma cell lines [52] and DLBCL xenograft models [53]
PD 1 inhibition	Pembrolizumab [35, 36]	PD 1 inhibitors have demonstrated promising activity in relapsed/refractory NKTL. Potential biomarkers that may allow better selection of patients for PD-1 inhibitors need to be explored
	Nivolumab [54]
CD38	Daratumumab [55]	Interim analysis of phase 2 study demonstrated 35.7% response in NKTL. CD38 status did not correlate with responses