This study aims to enroll non-small cell lung cancer patients who have undergone at least two rounds of standard treatment for drug resistance/recurrence. Patient-derived Organoid will be established, and drug sensitivity test will be conducted to intervene in the selection of clinical treatment plans. Efficacy evaluation and prognosis analysis will also be conducted. It is hoped that this study will provide a basis for the development of personalized treatment plans.

Twenty patients with drug-resistant/relapsed non-small cell lung cancer who met the inclusion criteria were enrolled in the study after signing an informed consent form. Tumor samples were obtained through clinical puncture, and qualified samples were subjected to organoid modeling. Perform drug sensitivity test on the established lung cancer organoids. The drugs used are all that have been marketed and applied in clinical practice. According to the results of organoid drug sensitivity analysis, the patient received a treatment plan with relatively sensitive drugs. Follow up prognostic data and relevant clinical information of enrolled patients, conduct statistical analysis on the consistency between drug sensitivity test results and patient treatment response, and evaluate the clinical effectiveness of treatment plans guided by organoid drug sensitivity results.

Inclusion Criteria:

1. Age ≥18 and ≤75 years old (calculated based on the date of signing informed consent);
2. Diagnosed as drug-resistant/relapsed non-small cell lung cancer;
3. After at least two systemic treatments and the disease progresses;
4. According to the efficacy evaluation criteria of solid tumors (RECIST 1.1), at least one lesion that has not received radiation therapy, has not received other local therapies, and can obtain tumor tissue (can be from a single lesion source or multiple lesions combined) is used for organoid establishment;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;
6. Expected survival time>3 months;
7. Before a tumor sample can be taken, there must be a record of disease progression on imaging after the previous treatment.;
8. The patient has informed consent and signed a written consent form;
9. The patients had good compliance and willingly followed the study plan, including scheduled visits, treatments, laboratory tests, and other research steps.

Exclusion Criteria:

1. Extremely weakened overall condition, unable to tolerate bronchoscopy examination;
2. Patients with acute suppurative inflammation of the respiratory tract accompanied by high fever, acute asthma attacks, and ongoing hemoptysis;
3. Have a history of interstitial lung disease, non infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc
4. Patients with active leptomeningeal disease or brain metastasis;
5. Diagnosed with other malignant diseases other than NSCLC within 5 years prior to initial administration (excluding curative basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curative resection of carcinoma in situ);
6. Have a history of immunodeficiency, including positive HIV serum tests;
7. Active hepatitis B without treatment (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center);
8. The presence of any serious or uncontrollable systemic diseases;
9. Pregnant or lactating female patients;
10. The researchers believe that patients who are not suitable to participate in this study.