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Phát triển lâm sàng của các chất ức chế thụ thể yếu tố tăng trưởng giống insulin-1 (IGF-1R): Điểm giao thoa?
Tóm tắt
Việc nhắm đến thụ thể yếu tố tăng trưởng giống insulin (IGF-1R) đã trở thành một trong những lĩnh vực được nghiên cứu nhiều nhất trong phát triển thuốc chống ung thư trong thập kỷ qua. Các chiến lược nhằm chặn hoạt động của IGF-1R bao gồm kháng thể đơn dòng, chất ức chế tyrosine kinase và kháng thể chống ligand. Sự nhiệt tình ban đầu nhanh chóng gặp phải nhiều thách thức. Thật không may, việc xác thực hiệu quả của các tác nhân nhắm đến IGF-1R trong các thử nghiệm lâm sàng quy mô lớn đã thất bại, tuy nhiên những hoạt động đơn lẻ có bằng chứng đã thấy trong các nghiên cứu ban đầu. Do đó, các câu hỏi về việc lựa chọn nhóm đối tượng mục tiêu phù hợp và thiết kế thử nghiệm thích hợp đang nổi lên. Mặc dù có hàng loạt các thử nghiệm lâm sàng được thực hiện, không có dấu hiệu sinh học dự đoán nào được xác thực cho đến giờ và các cơ chế kháng thuốc đối với các chất ức chế IGF-1R vẫn chưa rõ ràng. Một vấn đề khác cần giải quyết là cách tốt nhất để kết hợp các chất ức chế IGF-1R với các phương pháp điều trị khác. Bài tổng quan này nhấn mạnh các dữ liệu lâm sàng có liên quan nhất, nhấn mạnh các loại khối u chính mà việc ức chế IGF-1R cho thấy sự quan tâm tiềm năng. Chúng tôi cũng cố gắng rút ra dựa trên dữ liệu lâm sàng và chuyển tiếp một số dấu ấn sinh học ứng cử viên có thể giúp lựa chọn tốt hơn nhóm bệnh nhân có thể được hưởng lợi nhiều nhất từ phương pháp điều trị này.
Từ khóa
#thụ thể yếu tố tăng trưởng giống insulin #IGF-1R #ức chế IGF-1R #chống ung thư #dấu hiệu sinh họcTài liệu tham khảo
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