Targeting the JAK/STAT Pathway in T Cell Lymphoproliferative Disorders

Curr Hematol Malig Rep. 2019 Dec;14(6):570-576. doi: 10.1007/s11899-019-00545-5.

Abstract

Purpose of review: T cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize the current data describing the disruptions of JAK/STAT signaling in T cell malignancies and focus on the existing evidence for exploitation of this pathway with targeted therapies.

Recent findings: To date, preclinical studies have demonstrated the efficacy of JAK/STAT inhibition in the treatment of several T cell lymphoproliferative disorders. More recently, several early clinical trials have demonstrated promising results utilizing this approach as well. The benefit of the combination of JAK/STAT-targeted therapies along with immunotherapy and other molecularly targeted therapies is also discussed. There is substantial evidence that targeting the JAK/STAT pathway in T cell lymphoproliferative disorders could be of clinical benefit. There are several early clinical trials showing promise and many ongoing trials investigating the optimal utility of agents that inhibit this signaling pathway. In addition, targeting this pathway may provide a platform for further rational combination therapies.

Keywords: AITL; ALCL; CTCL; JAK; NK cell lymphoma; PTCL; STAT; T cell lymphoma; T cell lymphoproliferative disorders; T-ALL.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Diagnosis, Differential
  • Disease Management
  • Disease Susceptibility
  • Humans
  • Janus Kinases / metabolism*
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / metabolism*
  • Molecular Targeted Therapy* / methods
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / drug effects*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Treatment Outcome

Substances

  • STAT Transcription Factors
  • Janus Kinases