Objective:

To demonstrate the efficacy of patient-derived tumor organoids (PDTOs) in guiding personalized therapy for advanced lung adenocarcinoma with EGFR exon 21 L858R mutations, particularly in cases with prior treatment failures.

Key Findings:

• The patient achieved a partial response (PR) in lung lesions after PDTO-guided therapy, with a notable reduction in tumor size, despite previous treatment failures.
• PDTOs effectively recapitulated the tumor's biological characteristics and guided personalized treatment decisions.

Interpretation:

This case highlights the potential of PDTOs as a preclinical platform for individualized treatment strategies in advanced lung adenocarcinoma, particularly for patients with complex treatment histories, suggesting a need for further exploration in clinical settings.

Limitations:

• The study is based on a single case, limiting generalizability.
• Long-term outcomes and broader applicability of PDTO-guided therapy need further investigation.
• Future studies should include diverse patient demographics to enhance generalizability.

Conclusion:

PDTOs represent a promising approach for optimizing treatment in heavily pretreated lung cancer patients, potentially improving clinical outcomes and warranting further research into their application in clinical trials.