Isocitrate dehydrogenase mutations in gliomas: A review of current understanding and trials.
Isocitrate dehydrogenase mutations in gliomas: A review of current understanding and trials.
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DOI：
10.1093/noajnl/vdad053
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发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
Abdullah, Kalil G.
中科院分区：
文献类型：
--
作者：
Sharma, Nikhil;Mallela, Arka N.;Shi, Diana D.;Tang, Lilly W.;Abou-Al-Shaar, Hussam;Gersey, Zachary C.;Zhang, Xiaoran;McBrayer, Samuel K.;Abdullah, Kalil G.
异柠檬酸脱氢酶（IDH）是人体正常代谢和体内平衡的关键酶。然而，IDH的突变形式也是弥漫性胶质瘤的一个子集的定义特征。在这篇综述中，我们重点介绍了目前针对idh突变胶质瘤的技术，并总结了目前和已完成的探索这些策略的临床试验。我们讨论了多肽疫苗、突变型IDH （mIDH）抑制剂和PARP抑制剂的临床数据。肽疫苗具有独特的优势，可靶向患者肿瘤的特异性表位，诱导高度肿瘤特异性的CD4+ t细胞反应。另一方面，midh抑制剂专门针对癌细胞代谢中的突变IDH蛋白，从而有助于阻止胶质瘤的形成。我们还探讨了PARP抑制剂及其在治疗弥漫性胶质瘤中的作用，通过允许未修复的DNA复合物的持久性来利用idh突变的弥漫性胶质瘤。我们总结了针对弥漫性胶质瘤中IDH1和IDH2突变的各种已完成和当前的试验。针对突变型IDH的治疗在治疗进展性或复发性IDH突变型胶质瘤方面具有重要的前景，并可能在未来十年显著改变治疗模式。
Isocitrate dehydrogenase (IDH) is a key enzyme in normal metabolism and homeostasis. However, mutant forms of IDH are also defining features of a subset of diffuse gliomas. In this review, we highlight current techniques targeting IDH-mutated gliomas and summarize current and completed clinical trials exploring these strategies. We discuss clinical data from peptide vaccines, mutant IDH (mIDH) inhibitors, and PARP inhibitors. Peptide vaccines have the unique advantage of targeting the specific epitope of a patient’s tumor, inducing a highly tumor-specific CD4+ T-cell response. mIDH-inhibitors, on the other hand, specifically target mutant IDH proteins in cancer cell metabolism and thus help halt gliomagenesis. We also explore PARP inhibitors and their role in treating diffuse gliomas, which exploit IDH-mutant diffuse gliomas by allowing the persistence of unrepaired DNA complexes. We summarize various completed and current trials targeting IDH1 and IDH2 mutations in diffuse gliomas. Therapies targeting mutant IDH have significant promise in treating progressive or recurrent IDH-mutant gliomas and may significantly change treatment paradigms in the next decade.
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影响因子：
5.2
作者：
Pappula AL;Rasheed S;Mirzaei G;Petreaca RC;Bouley RA
通讯作者：
Bouley RA
影响因子：
7.5
作者：
Al-Khallaf H
通讯作者：
Al-Khallaf H
影响因子：
7.1
作者：
Mehani B;Asanigari S;Chung HJ;Dazelle K;Singh A;Hannenhalli S;Aldape K
通讯作者：
Aldape K
影响因子：
4.7
作者：
Kayabolen A;Yilmaz E;Bagci-Onder T
通讯作者：
Bagci-Onder T
DOI：
10.1158/1078-0432.ccr-21-0611
发表时间：
2021-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Mellinghoff IK;Penas-Prado M;Peters KB;Burris HA 3rd;Maher EA;Janku F;Cote GM;de la Fuente MI;Clarke JL;Ellingson BM;Chun S;Young RJ;Liu H;Choe S;Lu M;Le K;Hassan I;Steelman L;Pandya SS;Cloughesy TF;Wen PY
通讯作者：
Wen PY