Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.
Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.
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DOI：
10.3390/ijms241411684
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发表时间：
2023-07-20
影响因子：
5.6
通讯作者：
Zou, Yue
中科院分区：
文献类型：
--
作者：
Biswas, Himadri;Makinwa, Yetunde;Zou, Yue
关键词：
DNA损伤反应（DDR）被认为在癌症生长和治疗中具有重要作用。ATR（毛细血管扩张性共济失调突变和Rad3相关）激酶是DDR的主要调节因子，在癌症治疗中显示出显着的治疗潜力。ATR抑制剂已经显示出抗肿瘤的有效性，不仅作为单一疗法，而且还增强了标准化疗、放疗和免疫疗法的效果。ATR的生物学基础，以及其在癌症的发展和治疗中的功能意义，以及抑制这一目标作为治疗方法的理由，包括评估过去几十年的发展的进展和状态的有效和选择性ATR抑制剂的审查。这些抑制剂作为单一药物或与化疗，放疗和免疫治疗相结合的临床前和临床研究的当前应用也进行了充分的审查。本综述的结论与ATR抑制剂在临床前和临床背景下突出或确定的许多问题，以及提出的潜在补救措施的一些见解。
The DNA damage response (DDR) is recognized as having an important role in cancer growth and treatment. ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has shown significant therapeutic potential in cancer treatment. ATR inhibitors have shown anti-tumor effectiveness, not just as monotherapies but also in enhancing the effects of standard chemotherapy, radiation, and immunotherapy. The biological basis of ATR is examined in this review, as well as its functional significance in the development and therapy of cancer, and the justification for inhibiting this target as a therapeutic approach, including an assessment of the progress and status of previous decades’ development of effective and selective ATR inhibitors. The current applications of these inhibitors in preclinical and clinical investigations as single medicines or in combination with chemotherapy, radiation, and immunotherapy are also fully reviewed. This review concludes with some insights into the many concerns highlighted or identified with ATR inhibitors in both the preclinical and clinical contexts, as well as potential remedies proposed.
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