Glycyrrhizic Acid Alleviates Osimertinib‐Induced Cutaneous Toxicity by Inhibiting Keratinocyte Apoptosis and Inflammation

Osimertinib is a primary treatment for patients with EGFR-mutated non-small cell lung cancer. But a significant number of patients receiving Osimertinib treatment suffer from cutaneous toxicity, which includes symptoms such as rash, itching, and hair loss. This study aims to help clinical patients suffering from cutaneous toxicity to improve their quality of life. Mice treated with 50 mg/kg/day Osimertinib for 42 days exhibited different levels of cutaneous toxicity. PI/Annexin-V apoptosis assay and western blotting were used to assess keratinocyte apoptosis and DNA damage. Osimertinib upregulated inflammatory factors including CCL2, CCL27, and IL18. Glycyrrhizic acid (GA) is the most important active ingredient in licorice with pharmacological effects such as anti-inflammatory, antiviral, and anti-apoptotic. Due to its rich bioactivity, the research about GA has always been popular. However, the effects of it on relieving cutaneous toxicity have not been studied yet. We have explored the therapeutic effects and mechanisms of GA on keratinocytes and C57BL/6 mice. Thirty milligrams/kg/day of GA could effectively reduce the frequency and severity of cutaneous toxicity induced by Osimertinib, restore epidermal thickness in mice, reduce DNA damage, and lower the expression levels of inflammatory factors. Our results indicated that GA could potentially mitigate the cutaneous toxicity caused by Osimertinib, which could position it as a promising adjunct in clinical practice.