2023 World Conference on Lung Cancer (Posters)-P1.12. BiFeO3@PANI Sensitizes LKB1-Deficient LUAD to Radiotherapy via Induction of Tumoral Lipid Oxidation and Ferroptosis

P1.12. BiFeO3@PANI Sensitizes LKB1-Deficient LUAD to Radiotherapy via Induction of Tumoral Lipid Oxidation and Ferroptosis - PDF(Abstract)

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This research study presented at the WCLC 2023 conference investigates the role of ferroptosis in LKB1-deficient lung adenocarcinoma (LUAD) and explores a potential therapeutic approach to overcome ferroptosis resistance induced by radiotherapy.<br /><br />The study used genetically engineered mouse models of LUAD with LKB1 or p53 deletion. Single cell RNA sequencing analysis revealed that the profiles of tumor-infiltrating lymphocytes were reprogrammed in LKB1-deleted lung tumors, with fewer neutrophils and more B cells present. Gene set enrichment analysis predicted alterations in ferroptosis and lipid homeostasis due to LKB1 deletion.<br /><br />Furthermore, analysis of the Cancer Therapeutics Response Portal (CTRP) database identified 17 genes associated with ferroptosis resistance, and a positive correlation was found between LKB1 mutation and high ferroptosis resistance scores in TCGA LUAD datasets. In vitro experiments demonstrated that LKB1 loss resulted in reduced lipid oxidation and decreased sensitivity to ferroptosis agonists erastin and RSL3. However, treatment with BiFeO3@PANI increased lipid oxidation upon irradiation and significantly reduced cell proliferation.<br /><br />These findings suggest that LKB1 deficiency plays a role in cell resistance to ferroptosis induced by radiotherapy. Additionally, the study highlights the potential of BiFeO3@PANI as a therapeutic agent to overcome this resistance in LKB1-deficient LUAD.<br /><br />In summary, this research identifies LKB1 as a key driver of ferroptosis resistance in LUAD and proposes BiFeO3@PANI as a potential treatment strategy to sensitize LKB1-deficient tumors to radiotherapy-induced ferroptosis.

Asset Subtitle

Zeqin Guo

Meta Tag

Speaker Zeqin Guo

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

ferroptosis

LKB1-deficient lung adenocarcinoma

therapeutic approach

radiotherapy

genetically engineered mouse models

tumor-infiltrating lymphocytes

lipid homeostasis

ferroptosis resistance

BiFeO3@PANI

cell proliferation