Wee1激酶是参与细胞周期G₂/M检查点和DNA损伤修复过程的关键激酶。超过50%的肿瘤存在p53基因缺失或突变，导致细胞周期G₁/S检查点的缺陷，使得肿瘤细胞DNA的复制及损伤修复过程更依赖于G₂/M检查点。抑制Wee1激酶活性后，肿瘤细胞的DNA损伤不能及时修复便进入M期，造成基因组不稳定性和染色体缺失，引发有丝分裂灾难，导致肿瘤细胞凋亡。adavosertib是阿斯利康公司研发的小分子选择性Wee1激酶抑制剂，通过选择性抑制Wee1激酶，阻滞p53基因缺陷型肿瘤在G₂/M期检查点的DNA损伤修复，导致肿瘤细胞死亡，最终达到治疗肿瘤的目的。目前adavosertib单用或与其他抗癌药物联合的研究正处于I/Ⅱ期临床研究中，其有效性和安全性已经得到验证。

Wee1 is the key kinase in cell cycle G₂/M check point and DNA damage repair. P53 gene mutates in more than 50% of tumor cells and abrogates the G₁/S phase check point in cell cycle, which makes it more dependent on G₂/M check point. Once Wee1 is inhibited, tumor cell cycle enters M phase without repairing DNA damage timely. It causes genomic instability and chromosomal deletion, induces mitotic catastrophe and leads to the apoptosis of tumor cells. adavosertib is a kind of selective small molecule Wee1 inhibitors launched by AstraZeneca. adavosertib retards DNA damage repair of p53 mutated tumor cells on G₂/M check point, leads to the death of tumor, and achieves the goal of cancer treatment. At present, the phase I/Ⅱ clinical trials of adavosertib`s monotherapy and combination therapy with other anti-tumor drugs are in progress and its effectiveness and safety have been confirmed.

中国医学科学院医学与健康科技创新工程经费资助项目（2016-I2M-3-022、2017-I2M-2-019）