Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy.
Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy.
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DOI：
10.3390/cells11233717
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发表时间：
2022-11-22
期刊：
影响因子：
6
通讯作者：
Lipkowitz, Stanley
中科院分区：
文献类型：
--
作者：
Kundu, Manjari;Greer, Yoshimi Endo;Dine, Jennifer L.;Lipkowitz, Stanley
肿瘤坏死因子（TNF）超家族成员肿瘤坏死因子相关凋亡诱导配体（TRAIL）通过激活死亡受体（DR）诱导癌细胞凋亡，对正常细胞或组织几乎没有毒性。肿瘤坏死因子相关凋亡诱导配体（TRAIL）对肿瘤细胞凋亡的选择性激活作用使其具有理想的治疗特性，从而导致了许多DR激动剂的开发和临床试验。然而，TRAIL/DR靶向治疗在各种恶性肿瘤的临床试验中广泛无效，原因仍然知之甚少。三阴性乳腺癌（TNBC）是乳腺癌中预后最差的。靶向TRAIL DR途径在临床前模型中的TNBC亚组中显示出显著的功效，但在临床试验中再次未显示出明显的活性。在这篇综述中，我们将讨论的信号成分和机制管理TRAIL通路的激活和临床试验结果讨论的重点是TNBC。还讨论了在临床中使用DR激动剂的挑战和潜在的解决方案，包括考虑DR激动剂的药代动力学和药效学特性，通过预测生物标志物选择患者，以及潜在的联合治疗。此外，最近的研究结果TRAIL治疗对免疫反应的影响，以及新的策略来解决这些挑战，进行了讨论。
The tumor necrosis factor (TNF) superfamily member TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via death receptor (DR) activation with little toxicity to normal cells or tissues. The selectivity for activating apoptosis in cancer cells confers an ideal therapeutic characteristic to TRAIL, which has led to the development and clinical testing of many DR agonists. However, TRAIL/DR targeting therapies have been widely ineffective in clinical trials of various malignancies for reasons that remain poorly understood. Triple negative breast cancer (TNBC) has the worst prognosis among breast cancers. Targeting the TRAIL DR pathway has shown notable efficacy in a subset of TNBC in preclinical models but again has not shown appreciable activity in clinical trials. In this review, we will discuss the signaling components and mechanisms governing TRAIL pathway activation and clinical trial findings discussed with a focus on TNBC. Challenges and potential solutions for using DR agonists in the clinic are also discussed, including consideration of the pharmacokinetic and pharmacodynamic properties of DR agonists, patient selection by predictive biomarkers, and potential combination therapies. Moreover, recent findings on the impact of TRAIL treatment on the immune response, as well as novel strategies to address those challenges, are discussed.
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DOI：
10.1158/1078-0432.ccr-20-0251
发表时间：
2020-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Aboulnasr F;Krogman A;Graham RP;Cummins NW;Misra A;Garcia-Rivera E;Anderson JR;Natesampillai S;Kogan N;Aravamudan M;Nie Z;Chung TDY;Buick R;Feldman AL;King RL;Novak AJ;Ansell SM;Kenderian S;Badley AD
通讯作者：
Badley AD
癌症中的白细胞介素：从生物学到治疗。
DOI：
10.1038/s41568-021-00363-z
发表时间：
2021-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Briukhovetska D;Dörr J;Endres S;Libby P;Dinarello CA;Kobold S
通讯作者：
Kobold S
影响因子：
45.3
作者：
Bibeau, Frederic;Lopez-Crapez, Evelyne;Boissiere-Michot, Florence
通讯作者：
Boissiere-Michot, Florence
DOI：
10.1186/bcr3645
发表时间：
2014-04-17
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Garimella SV;Gehlhaus K;Dine JL;Pitt JJ;Grandin M;Chakka S;Nau MM;Caplen NJ;Lipkowitz S
通讯作者：
Lipkowitz S
影响因子：
3.7
作者：
An D;Kim K;Kim J
通讯作者：
Kim J