2023 World Conference on Lung Cancer (Posters)-EP09.02. Fibrates Enhances Radiotherapy Efficacy by Elevating HDL Levels to Induce Tumor Cell Ferroptosis in NSCLC with Brain Metastasis

EP09.02. Fibrates Enhances Radiotherapy Efficacy by Elevating HDL Levels to Induce Tumor Cell Ferroptosis in NSCLC with Brain Metastasis - PDF(Slides)

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A study conducted by researchers in China has found that fibrates, a class of drugs used to lower cholesterol levels, can enhance the efficacy of radiotherapy in non-small cell lung cancer (NSCLC) patients with brain metastases. The study aimed to investigate the relationship between lipid levels and the effectiveness of radiotherapy in NSCLC patients with brain metastases, in order to find new treatment strategies. <br /><br />The researchers collected clinical information from 78 NSCLC patients with brain metastases and analyzed the relationship between blood lipids and the efficacy of brain radiotherapy. They found that elevated levels of high-density lipoprotein (HDL) and normal levels of cholesterol were associated with longer progression-free survival (PFS) and overall survival (OS) in these patients. Non-targeted metabolomics assays revealed that the suppression of PPARα may be responsible for the abnormalities in HDL and cholesterol levels in these patients. <br /><br />Further experiments in cellular and animal models showed that fenofibrate, a fibrate drug, could promote HDL synthesis and induce ferroptosis, a type of cell death caused by increased iron levels, in tumor cells treated with ionizing radiation. Lipidomic assays revealed changes in fatty acid composition within tumor cells, which may contribute to the sensitizing effect of radiotherapy. <br /><br />Additionally, the study found that fenofibrate combined with radiotherapy increased the infiltration of CD8 T cells within the tumor microenvironment, indicating enhanced efficacy of immunotherapy. This combination treatment showed potential as a therapeutic strategy for NSCLC patients with brain metastases. <br /><br />In conclusion, the study suggests that blood HDL and total cholesterol levels are correlated with the efficacy of brain radiotherapy in NSCLC patients. Modulating HDL levels can alter fatty acid composition, induce ferroptosis, and enhance the sensitizing effect of radiotherapy. Furthermore, this combination treatment can improve the efficacy of immunotherapy by increasing CD8 T cell infiltration. Therefore, fenofibrate combined with radiotherapy and immunotherapy may be a promising therapeutic strategy for NSCLC patients with brain metastases.

Asset Subtitle

Xiaorong Dong

Meta Tag

Speaker Xiaorong Dong

Topic Metastatic NSCLC: Local Therapies - Integration With Systemic Therapies

Keywords

fibrates

cholesterol levels

radiotherapy

NSCLC

brain metastases

HDL

fenofibrate

ferroptosis

tumor cells

immunotherapy