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
From: Molecular pathogenic pathways in extranodal NK/T cell lymphoma
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] |