Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model

Area of Science:

• Oncology
• Nutritional Biochemistry
• Pharmacology

Background:

• Selenium (Se) and fish oil (FO) exhibit anti-epidermal growth factor receptor (EGFR) activity.
• EGFR inhibitors like gefitinib and erlotinib are used in lung cancer treatment.
• Nutritional supplements may potentiate conventional cancer therapies.

Purpose of the Study:

• To compare the anti-cancer efficacy of gefitinib and erlotinib alone versus in combination with Se/FO.
• To investigate the effects of Se/FO on signaling pathways and tumor progression in lung cancer.
• To evaluate the impact of combined therapy on immune checkpoint molecules.

Main Methods:

• Lewis LLC1 tumor-bearing mice were treated with vehicle, Se/FO, gefitinib, erlotinib, or combinations.
• Tumor tissues were analyzed for mRNA and protein expression of key signaling and immune molecules.
• Tumor growth, metastasis, angiogenesis, stemness, and cell cycle markers were assessed.

Main Results:

• Combination treatment with Se/FO and EGFR inhibitors significantly reduced tumor volume, weight, and metastasis compared to monotherapy.
• Combined therapy modulated multiple signaling pathways, including reduced EGFR, Wnt, and β-catenin, and increased GSK-3β.
• Immune checkpoint molecules (PD-1, PD-L1, CTLA-4) were downregulated, while immune activation markers (NKp46, CD28, IL-2) were upregulated.

Conclusions:

• Se/FO enhances the therapeutic efficacy of gefitinib and erlotinib in a lung cancer mouse model.
• The combination therapy acts through modulation of diverse signaling pathways, immune checkpoints, and tumor microenvironment.
• This suggests a potential synergistic effect of nutritional supplements with EGFR inhibitors for lung cancer treatment.