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Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma

Tetsuya Sekita1,2, Tesshi Yamada3, Eisuke Kobayashi4

  • 1Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Cancers
|May 21, 2020
PubMed
Abstract

Insights

Targeting Traf2-and-Nck-interacting kinase (TNIK) shows promise for metastatic synovial sarcoma treatment. A small molecule inhibitor, NCB-0846, effectively reduced tumor growth by blocking Wnt signaling pathways crucial for cancer cell survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Metastatic synovial sarcoma treatment remains challenging, necessitating novel molecular therapeutics.
  • Dysregulation of Wnt signaling pathways is implicated in synovial sarcoma pathogenesis.
  • Traf2-and-Nck-interacting kinase (TNIK) is a key transcriptional co-regulator of Wnt target genes.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting TNIK in synovial sarcoma.
  • To evaluate the efficacy of a small interfering RNA (siRNA) targeting TNIK and a small-molecule TNIK inhibitor, NCB-0846.

Main Methods:

  • TNIK expression was quantified in 20 clinical synovial sarcoma samples.
  • The efficacy of NCB-0846 was assessed in four synovial sarcoma cell lines and a mouse xenograft model.

Main Results:

  • Synovial sarcoma cell lines with Wnt activation demonstrated a strong dependence on TNIK for proliferation and survival.
  • NCB-0846 induced apoptosis in synovial sarcoma cells by inhibiting Wnt target genes, including MYC.
  • Oral administration of NCB-0846 led to the regression of synovial sarcoma xenografts.

Conclusions:

  • Wnt signaling activation is causally involved in synovial sarcoma development.
  • TNIK inhibition presents a novel therapeutic strategy for synovial sarcoma, with NCB-0846 demonstrating significant anti-tumor activity.
Keywords:
MYCNCB-0846TNIKWnt signalingsynovial sarcoma

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