第1周
医学
生物标志物
癌症
癌症研究
肿瘤科
生物信息学
内科学
生物
细胞周期
细胞周期蛋白依赖激酶1
生物化学
作者
Siqing Fu,Yudong Wang,Khandan Keyomarsi,Funda Meric-Bernstein
标识
DOI:10.1080/13543784.2018.1511700
摘要
Wee1 kinase controls the G2-M checkpoint. Wee1 inhibition by AZD1775 allows cells with a deregulated G1 checkpoint to progress, resulting in catastrophe and apoptosis. The challenges ahead are in the establishment of the optimum dosing schedule either alone or in combination and the identification of patients with specific biomarker profiles who benefit most.This article provides an overview of AZD1775, based on English peer-reviewed articles on MEDLINE. The authors highlight the data from the published preclinical and clinical studies.A majority of the current clinical trials focus on AZD1775 combined with chemotherapy or radiation. Treatment with AZD1775 was tolerated, and antitumor activity has been observed, especially in patients with advanced malignancies harboring G1 checkpoint aberrations and/or DNA damage repair defects. Thus, identification of the molecular subtypes that benefit most from the treatment with AZD1775 alone or in combination may provide a novel strategy for cancer therapy. Research is needed for devising regimens to explore AZD1775 in combination with biologically targeted agents and/or immunotherapy (low dose vs. high dose, intermittent vs. continuous, sequential vs. concurrent, etc.) for identifying potential biomarkers predictive of response and survival.
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