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09:52

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Published on: December 4, 2018

The calcineurin/NFAT signaling pathway: a novel therapeutic target in leukemia and solid tumors

Hind Medyouf1, Jacques Ghysdael

  • 1CNRS UMR146 and Institut Curie, Centre Universitaire, Orsay, France.

Cell Cycle (Georgetown, Tex.)
|February 1, 2008
PubMed

Insights

Persistent activation of the calcineurin/NFAT pathway promotes cancer in mouse models. This pro-oncogenic signaling can be effectively targeted using calcineurin inhibitors, offering a potential therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • The calcineurin/NFAT pathway is crucial for vertebrate development and integrates calcium signals with other pathways like MAPkinase, WNT, and NOTCH.
  • Dysregulation of this pathway is implicated in various cancers, including solid tumors, lymphoma, and lymphoid leukemia.

Purpose of the Study:

  • To investigate the role of calcineurin/NFAT signaling in T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma.
  • To evaluate the therapeutic potential of calcineurin inhibitors in targeting oncogenic calcineurin/NFAT signaling.

Main Methods:

  • Utilized mouse models of human T-ALL/lymphoma.
  • Analyzed the effects of persistent calcineurin/NFAT pathway activation in vivo.
  • Assessed the efficacy of calcineurin inhibitors.

Main Results:

  • Demonstrated that sustained calcineurin/NFAT signaling is pro-oncogenic in mouse models of T-ALL/lymphoma.
  • Showed that calcineurin inhibitors effectively target this oncogenic pathway in vivo.

Conclusions:

  • Persistent calcineurin/NFAT pathway activation drives oncogenesis in T-ALL/lymphoma.
  • Calcineurin inhibitors represent a promising therapeutic approach for cancers with deregulated calcineurin/NFAT signaling.

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