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Table 1 This table describes the genes implicated in the pathogenesis of NKTL and the potential therapeutic targets

From: Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL)

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