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Nhắm mục tiêu p53 bằng các phân tử nhỏ trong các loại ung thư huyết học
Tóm tắt
p53 là một chất ức chế khối u mạnh mẽ và là một mục tiêu điều trị ung thư hấp dẫn. Một bước đột phá trong nghiên cứu ung thư đến từ việc phát hiện ra các loại thuốc có khả năng tái kích hoạt chức năng của p53. Hầu hết các tác nhân chống ung thư, từ hóa trị liệu và xạ trị truyền thống đến các phân tử nhỏ không peptide vừa mới được phát triển gần đây, đều phát huy tác dụng của chúng bằng cách tăng cường hoạt động chống sinh sản của p53. Các phân tử nhỏ như nutlin, RITA và PRIMA-1 có thể kích hoạt p53 đã chứng minh được hiệu quả chống khối u của chúng trong nhiều loại bệnh ung thư huyết học khác nhau. Quan trọng là, nutlin và PRIMA-1 đã thành công trong việc đạt đến giai đoạn thử nghiệm lâm sàng giai đoạn I/II ở ít nhất một loại ung thư huyết học. Do đó, việc kích hoạt dược lý p53 thông qua các phân tử nhỏ này có ảnh hưởng lớn đến việc sử dụng dự đoán và thiết kế thuốc nhắm mục tiêu. Trong bài tổng quan hiện tại, chúng tôi trình bày những thành tựu gần đây về nghiên cứu p53 sử dụng các phân tử nhỏ trong các bệnh ung thư huyết học. Hoạt động chống ung thư của các lớp hợp chất khác nhau nhắm mục tiêu vào con đường tín hiệu p53 và cơ chế tác động của chúng sẽ được thảo luận. Ngoài ra, chúng tôi cũng thảo luận về cách mà protein ức chế khối u p53 hứa hẹn là một mục tiêu thuốc cho các liệu pháp mới gần đây và trong tương lai cho các bệnh này.
Từ khóa
#p53 #thuốc chống ung thư #ung thư huyết học #phân tử nhỏ #kích hoạt p53Tài liệu tham khảo
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