Related Experiment Videos

Therapeutic implications of peroxisome proliferator-activated receptors in non-small cell lung cancer

Li Nie1, Xinliang Zou2,3,4, Huaxi Liu5

  • 1School of Medicine, Chongqing University, Chongqing, 400030, China.

Discover Oncology
|July 20, 2026
PubMed

Insights

Peroxisome proliferator-activated receptors (PPARs) show dual roles in non-small cell lung cancer (NSCLC), acting as either tumor suppressors or promoters. Understanding their context-dependent functions is key for developing targeted NSCLC therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolism

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality, with persistent challenges in drug resistance and treatment outcomes.
  • Peroxisome proliferator-activated receptors (PPARs), including PPARα, PPARβ/δ, and PPARγ, are transcription factors regulating lipid metabolism and inflammation, with dysregulated expression in NSCLC.
  • The dual role of PPAR isoforms in NSCLC (tumor-suppressive vs. tumor-promoting) creates complexity, influenced by cellular context, metabolic state, and genetic background.

Purpose of the Study:

  • To critically review the isoform-specific functions and molecular mechanisms of PPARs in NSCLC.
  • To summarize preclinical and clinical advances in PPAR-targeted strategies for NSCLC prevention and treatment.
  • To provide a framework for developing precision therapies that address the context-dependent nature of PPAR signaling in NSCLC.

Main Methods:

  • Literature review of preclinical and clinical studies on PPARs in NSCLC.
  • Analysis of molecular mechanisms underlying PPAR isoform functions in different NSCLC contexts.
  • Evaluation of current and emerging PPAR-targeted therapeutic strategies, including combinations with immunotherapy.

Main Results:

  • PPARs integrate metabolic, inflammatory, and immune signals, highlighting their role at the intersection of metabolism and anti-tumor immunity in NSCLC.
  • Conflicting evidence exists regarding PPAR isoform functions, with all three potentially exerting tumor-suppressive or tumor-promoting effects.
  • Clinically available PPAR agonists are under investigation in combination therapies, emphasizing the need for biomarker-guided patient selection.

Conclusions:

  • The context-dependent duality of PPAR signaling in NSCLC necessitates a nuanced approach for therapeutic development.
  • Understanding PPAR isoform-specific functions and mechanisms is crucial for advancing precision medicine in NSCLC.
  • Further research is needed to bridge translational gaps and optimize PPAR-targeted strategies for NSCLC treatment and prevention.
Keywords:
Anticancer therapyLipid metabolismNon-small cell lung cancerPeroxisome proliferator-activated receptors

Related Concept Videos

Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...