AXL-mRNA Overexpression in Size-Based Enriched Circulating Tumor Cells as a Potential Biomarker for Anti-AXL Targeted...

Area of Science:

• Oncology
• Molecular Biology
• Biomarkers

Background:

• AXL receptor tyrosine kinase is implicated in cancer progression, metastasis, and therapeutic resistance.
• AXL signaling pathways are crucial in epithelial-to-mesenchymal transition (EMT), cell survival, and invasion.
• Emerging AXL inhibitors show promise in clinical trials for non-small cell lung cancer (NSCLC).

Purpose of the Study:

• To investigate AXL-mRNA overexpression in circulating tumor cell (CTC) fractions of NSCLC patients.
• To assess AXL-mRNA levels in patients receiving osimertinib or immunotherapy.
• To explore the potential of AXL-mRNA as a predictive biomarker for targeted therapies.

Main Methods:

• Circulating tumor cells (CTCs) were enriched using size-based methods (Parsortix).
• AXL-mRNA overexpression was quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
• Patient cohorts included NSCLC patients undergoing osimertinib treatment (n=39) or immunotherapy (n=116).

Main Results:

• AXL-mRNA overexpression in CTCs was detected at various time points in both treatment groups.
• In the osimertinib group, overexpression ranged from 8.9% to 16.1% across different treatment stages.
• In the immunotherapy group, overexpression was observed before and during treatment (6.9% to 11.3%), but not at disease progression.

Conclusions:

• AXL-mRNA overexpression in CTC fractions is detectable in NSCLC patients.
• These findings suggest AXL-mRNA may serve as a potential biomarker.
• Further large-scale clinical studies are warranted to validate AXL-mRNA as a biomarker for anti-AXL therapies in NSCLC.