Glycyrrhizic Acid Alleviates Osimertinib-Induced Cutaneous Toxicity by Inhibiting Keratinocyte Apoptosis and...

Area of Science:

• Oncology
• Dermatology
• Pharmacology

Background:

• Osimertinib is a key treatment for EGFR-mutated non-small cell lung cancer (NSCLC).
• A significant number of NSCLC patients experience cutaneous toxicity (rash, itching, hair loss) during Osimertinib therapy.
• Current management strategies for Osimertinib-induced skin toxicity require further improvement to enhance patient quality of life.

Purpose of the Study:

• To investigate the therapeutic potential of Glycyrrhizic acid (GA) in mitigating Osimertinib-induced cutaneous toxicity.
• To explore the underlying mechanisms by which GA affects keratinocyte apoptosis, DNA damage, and inflammatory responses.

Main Methods:

• C57BL/6 mice were treated with Osimertinib (50 mg/kg/day) for 42 days to induce cutaneous toxicity.
• PI/Annexin-V apoptosis assay and western blotting were employed to evaluate keratinocyte apoptosis and DNA damage.
• The expression levels of inflammatory factors (CCL2, CCL27, IL18) were assessed.
• Mice received co-treatment with GA (30 mg/kg/day) to determine its protective effects.

Main Results:

• Osimertinib treatment led to varying degrees of cutaneous toxicity in mice.
• Osimertinib upregulated key inflammatory factors, including CCL2, CCL27, and IL18.
• GA treatment (30 mg/kg/day) significantly reduced the frequency and severity of cutaneous toxicity.
• GA restored epidermal thickness, decreased DNA damage, and lowered inflammatory factor expression in Osimertinib-treated mice.

Conclusions:

• Glycyrrhizic acid demonstrates significant potential in alleviating Osimertinib-induced cutaneous toxicity.
• GA's anti-inflammatory and anti-apoptotic properties contribute to its protective effects on skin.
• GA may serve as a promising adjunctive therapy to improve the quality of life for NSCLC patients undergoing Osimertinib treatment.