Therapeutic Targeting of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway in Cutaneous T-Cell Lymphoma

Authors

Alisha Kashyap
Julia Dai
Xiao Ni

Publication Date

2-7-2025

Journal

Cancers

Abstract

Background/Objectives: Cutaneous T-cell lymphoma (CTCL) is a rare group of non-Hodgkin lymphomas characterized by the clonal expansion of malignant T cells. While current treatments can alleviate symptoms and significant progress has been made in treating leukemic CTCL, a definitive cure remains elusive. Dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a key driver of CTCL pathogenesis. As a result, therapeutic strategies targeting JAK/STAT signaling have gained momentum, with the increasing use of JAK inhibitors and other agents that effectively suppress this pathway. These immune-modulating therapies have broad effects on physiological processes, inflammation, and the pathological changes associated with both inflammatory diseases and cancers. Several JAK inhibitors, originally FDA-approved for inflammatory conditions, are now being investigated for cancer treatment.

Methods: In this paper, a brief review of the literature on JAK/STAT pathway dysregulation in CTCL is provided, highlighting both clinical and preclinical studies involving JAK inhibitors and other agents that target this pathway.

Results: Specifically, we focus on six JAK inhibitors currently under clinical investigation-golidocitinib, ruxolitinib, cerdulatinib, tofacitinib, upadacitinib, and abrocitinib. Additionally, we discuss preclinical studies that explore the mechanisms underlying JAK/STAT pathway inhibition in CTCL. Furthermore, we review reported cases in which CTCL relapsed or emerged following JAK inhibitor treatment.

Conclusions: Collectively, these findings support the potential clinical utility of targeting the JAK/STAT pathway in CTCL. However, further research is needed to evaluate safety risks, minimize adverse effects, and optimize these therapeutic strategies.

Keywords

JAK/STAT inhibitors, JAK/STAT pathway, Sézary syndrome, adverse effects, clinical response, cutaneous T-cell lymphoma, mycosis fungoides, pathogenesis, therapeutic strategies

DOI

10.3390/cancers17040568

PMID

40002165

PMCID

PMC11853177

PubMedCentral® Posted Date

2-7-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes