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Expert Opin Investig Drugs. 2005 Jun;14(6):557-68.

Peroxisome proliferator-activated receptor-gamma ligands for the treatment of breast cancer.

Author information

1
Charité School of Medicine, Department of Oncology and Haematology, Humboldt University, Berlin, Germany. martin.fenner@charite.de

Abstract

Pioglitazone and rosiglitazone are thiazolidinediones used for the treatment of Type 2 diabetes mellitus. They modulate glucose and fat metabolism, mainly by binding to the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma signalling is involved in a number of other disease conditions including cancer. In breast cancer cells, PPAR-gamma ligands inhibit proliferation and induce apoptosis both in vitro and in vivo. PPAR-gamma ligands also inhibit tumour angiogenesis and invasion. The only published clinical trial using a PPAR-gamma ligand in patients with metastatic breast cancer failed to show any clinical benefits. The mechanism of action of the thiazolidinediones in breast cancer cells is not fully understood but involves interactions with other nuclear hormone receptors, transcriptional co-activators and repressors as well as PPAR-gamma-independent effects. A better understanding of these mechanisms will be needed before PPAR-gamma ligands may be useful in the treatment of breast cancer patients.

PMID:
16004588
DOI:
10.1517/13543784.14.6.557
[Indexed for MEDLINE]

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