PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Lung cancer remains a leading cause of cancer mortality globally.
• Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulating key cellular processes.
• PPARγ activation has demonstrated both anti-tumor and pro-tumor effects in lung cancer contexts.

Purpose of the Study:

• To review the dual role of PPARγ modulators in lung cancer.
• To consolidate the molecular mechanisms underlying PPARγ's effects on tumor and stromal cells.
• To discuss the clinical prospects and challenges of PPARγ agonists in lung cancer therapy.

Main Methods:

• Literature review of preclinical and clinical studies on PPARγ in lung cancer.
• Analysis of molecular mechanisms of PPARγ activation and its targets.
• Evaluation of clinical data regarding PPARγ agonists' efficacy and toxicity.

Main Results:

• PPARγ activation inhibits lung cancer cell proliferation, induces apoptosis, and reduces invasion.
• PPARγ activation can promote tumor growth by affecting myeloid cells in the tumor microenvironment.
• PPARγ agonists show potential as lung cancer therapeutics, with synergistic effects with chemotherapy/radiotherapy.

Conclusions:

• PPARγ agonists offer a promising therapeutic avenue for lung cancer, but their clinical use is hampered by adverse effects.
• Further investigation into PPARγ's complex roles in both tumor and microenvironment is crucial.
• Balancing efficacy and toxicity through refined therapeutic strategies is essential for clinical success.