DNA损伤修复,治疗癌症 z-bo 2020-10-23 367

　　At present, cancer therapy targeting specific molecular defects caused by tumor cell mutations is the focus of many anti-cancer drug development. However, due to the lack of good targets and the genetic variation characteristics of tumors, platinum-based chemotherapy is still the main treatment for many cancers. The p53 gene is mutated in most cancers, which makes tumor cells resistant to platinum-based chemotherapy. However, using a phenomenon called synthetic lethality, it is still possible to selectively kill tumor cells by targeting the second gene.

　　Professor Michael Yaffe, director of the MIT Center for Precision Cancer Medicine, focuses on understanding and targeting cell signal transduction in cancer, aiming to find signal pathways that lead to synthetic lethality and develop treatment methods. His research team found in a recent study that MK2 protein is a key signaling molecule in cancer cells, and as a chaperone of p53 mediates the lethal effect of synthesis.

　　related results were published in the recent "Nature Communications" magazine.

　　P53 has two functions: first, by suspending cell division, so that cells have time to repair DNA damage; second, if the DNA damage is too severe, it will induce cell death. Platinum-based chemotherapy works by inducing enough DNA damage to initiate the cell's self-destruct mechanism. In previous work, Yaffe's lab found that when cancer cells lose p53, they can reconnect their signal transduction circuit to recruit MK2 as a backup route. However, MK2 only restores the ability to coordinate DNA damage repair, and cannot trigger cell death.

　　Yaffe's research team believes that targeting MK2 can create the effect of killing p53 mutant tumors by blocking the ability to coordinate DNA repair after chemotherapy. In preclinical models of non-small cell lung cancer tumors with p53 mutations, it was demonstrated that silencing MK2 combined with chemotherapy can lead to significant tumor shrinkage.