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Thí nghiệm độ nhạy hóa trị ex vivo sử dụng organoid ung thư buồng trứng nguyên phát để dự đoán phản ứng lâm sàng và sàng lọc thuốc hiệu quả
Tóm tắt
Việc lựa chọn phương pháp điều trị tốt nhất cho từng bệnh nhân ung thư đã thu hút sự chú ý nhằm cải thiện kết quả lâm sàng. Tiến bộ gần đây trong nuôi cấy organoid có thể dẫn đến sự phát triển của y học cá thể hóa. Khác với các loại thuốc nhắm vào phân tử, hiện chưa có phương pháp dự đoán phản ứng của bệnh nhân đối với hóa trị tiêu chuẩn trong ung thư buồng trứng. Chúng tôi đã chuẩn bị organoid bằng phương pháp spheroid xuất phát từ mô ung thư (CTOS) từ 61 bệnh nhân ung thư buồng trứng với tỷ lệ thành công 100%. Các bài kiểm tra độ nhạy hóa trị cho paclitaxel và carboplatin được thực hiện với tỷ lệ thành công 84% bằng cách sử dụng organoid nguyên phát từ 50 bệnh nhân đã được hóa trị. Một loạt độ nhạy khác nhau đã được quan sát thấy giữa các organoid đối với cả hai loại thuốc. Tất cả bốn organoid kháng trị lâm sàng đều kháng cả hai loại thuốc trong 18 trường hợp mà thông tin phản ứng lâm sàng có sẵn. Năm trong số 18 trường hợp (28%) là kháng kép, tỷ lệ phản ứng của chúng tương thích với tỷ lệ remiss lâm sàng. Carboplatin có độ nhạy cao hơn đáng kể trong các loại tế bào dạng dịch hơn là kiểu tế bào trong suốt (P = 0,025). Chúng tôi đã tạo ra hai dòng organoid, sàng lọc 1135 loại thuốc, và tìm thấy một số loại thuốc có hiệu quả kết hợp tốt hơn với carboplatin so với paclitaxel. Một số loại thuốc, bao gồm afatinib, đã cho thấy hiệu ứng bổ sung với carboplatin. Thí nghiệm độ nhạy organoid không dự đoán được kết quả lâm sàng, cả về thời gian sống không tiến triển lẫn tổng sống sót.
Từ khóa
#ung thư buồng trứng #organoid #hóa trị #độ nhạy #thuốc điều trịTài liệu tham khảo
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