Expanding role of PI5P4Ks in cancer: A promising druggable target.
Expanding role of PI5P4Ks in cancer: A promising druggable target.
复制标题
PI5P4K在癌症中的扩大作用：一个有前途的可毒靶。
DOI：
10.1002/1873-3468.14237
复制
发表时间：
2022-01
期刊：
影响因子：
3.5
通讯作者：
Emerling, Brooke M.
中科院分区：
文献类型：
--
作者：
Arora, Gurpreet K.;Palamiuc, Lavinia;Emerling, Brooke M.
癌细胞受到无数微环境压力的挑战，但它们有效适应不断变化的营养、能量、氧化和/或免疫环境的能力使它们能够生存和增殖。然而，这种适应性导致了独特的脆弱性，这些脆弱性是有吸引力的治疗靶点。PI 5 P4 K是磷酸肌醇激酶家族，是可药用的应激调节激酶，其作为代谢适应成为条件性必需的，为靶向癌细胞依赖性铺平了道路。此外，PI 5 P4 K与肿瘤抑制因子p53具有合成的致死相互作用，肿瘤抑制因子p53的缺失是许多癌症中恶性转化的最普遍的遗传驱动因素之一。PI 5 P4 K作为癌症中磷酸肌醇信号传导的扩展景观中的关键轴的出现已经刺激了针对这些酶的抑制剂的开发。因此，未来充分了解PI 5 P4 Ks功能生物学的研究将允许有针对性和有效的治疗干预。在这里，我们将尝试总结PI 5 P4 Ks在癌症中的作用，包括靶向它们是治疗脆弱性和有希望的多种癌症亚型的下一个治疗方法的证据。
Cancer cells are challenged by a myriad of microenvironmental stresses but their ability to efficiently adapt to the constantly changing nutrient, energy, oxidative and/or immune landscape allows them to survive and proliferate. Such adaptations, however, result in distinct vulnerabilities that are attractive therapeutic targets. PI5P4Ks, a family of phosphoinositide kinases, are druggable stress-regulated kinases that become conditionally essential as a metabolic adaptation, paving the way to targeting cancer cell dependencies. Further, PI5P4Ks have a synthetic lethal interaction with the tumor suppressor p53, the loss of which is one of the most prevalent genetic drivers of malignant transformation in many cancers. PI5P4K’s emergence as a crucial axis in the expanding landscape of phosphoinositide signaling in cancer has already stimulated the development of inhibitors targeting these enzymes. Thus, future investigations to fully understand the functional biology of the PI5P4Ks will allow for targeted and effective therapeutic interventions. Here we will attempt to summarize the mounting roles of the PI5P4Ks in cancer, including evidence that targeting them is a therapeutic vulnerability and promising next in line treatment for multiple cancer subtypes.
登录
查看更多内容
DOI：
10.1016/j.biocel.2013.03.009
发表时间：
2013-07-01
影响因子：
4
作者：
Elouarrat, Dalila;van der Velden, Yme U.;Haramis, Anna-Pavlina G.
通讯作者：
Haramis, Anna-Pavlina G.
影响因子：
--
作者：
Bulley, Simon J;Clarke, Jonathan H;Droubi, Alaa;Giudici, Maria-Luisa;Irvine, Robin F
通讯作者：
Irvine, Robin F
DOI：
10.1042/bj20130488
发表时间：
2013-08-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Clarke JH;Irvine RF
通讯作者：
Irvine RF
影响因子：
254.7
作者：
Gamboa, Adriana C.;Gronchi, Alessandro;Cardona, Kenneth
通讯作者：
Cardona, Kenneth
影响因子：
4.1
作者：
Bultsma, Yvette;Keune, Willem-Jan;Divecha, Nullin
通讯作者：
Divecha, Nullin