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Peroxisome proliferator-activated receptor-gamma in lung cancer: defining specific versus "off-target" effectors

Raphael A Nemenoff1

  • 1Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Raphael.Nemenoff@UCHSC.edu

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|November 3, 2007
PubMed

Insights

Thiazolidinediones (TZDs) show promise in preventing lung cancer by inhibiting tumor growth. However, their chronic use may increase cardiovascular risks, necessitating further research into their mechanisms of action.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Thiazolidinediones (TZDs) like rosiglitazone and pioglitazone are known to inhibit tumor growth, progression, and metastasis.
  • These drugs are agonists for peroxisome proliferator-activated receptor-gamma (PPAR gamma) and influence other cellular pathways.
  • Previous research indicates TZDs can induce apoptosis and inhibit lung cancer growth in xenograft models, with retrospective studies suggesting chemopreventive potential.

Purpose of the Study:

  • To review the mechanisms of thiazolidinediones (TZDs) in lung cancer, focusing on both anti-tumorigenic and cardiovascular effects.
  • To elucidate the relative contributions of PPAR gamma-dependent and PPAR gamma-independent pathways in mediating TZD effects.
  • To assess the potential of TZDs as chemopreventive agents for lung cancer.

Main Methods:

  • Review of existing literature on thiazolidinediones (TZDs) and their effects on cancer.
  • Analysis of studies investigating PPAR gamma-dependent and independent pathways.
  • Examination of data from xenograft models and retrospective clinical studies.

Main Results:

  • TZDs demonstrate anti-tumorigenic properties, including inhibition of tumor growth, progression, and metastasis in lung cancer models.
  • Retrospective data suggest a reduced lung cancer risk associated with TZD use.
  • Emerging evidence links chronic TZD use to an increased risk of adverse cardiovascular events.

Conclusions:

  • TZDs exhibit significant potential for lung cancer chemoprevention through both PPAR gamma-dependent and independent mechanisms.
  • Understanding the dual role of TZDs in cancer and cardiovascular health is critical.
  • Further research is needed to balance the anti-cancer benefits against potential cardiovascular risks.

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