Article
Biochemistry & Molecular Biology
Dong Chen, Siyuan Xia, Rukang Zhang, Yuancheng Li, Christopher A. Famulare, Hao Fan, Rong Wu, Mei Wang, Allen C. Zhu, Shannon E. Elf, Rui Su, Lei Dong, Martha Arellano, William G. Blum, Hui Mao, Sagar Lonial, Wendy Stock, Olatoyosi Odenike, Michelle Le Beau, Titus J. Boggon, Chuan He, Jianjun Chen, Xue Gao, Ross L. Levine, Jing Chen
Summary: The study revealed that mutant IDH2 in AML cells commonly has K413 acetylation, which negatively regulates its activity by attenuating dimerization and blocking substrate and cofactor binding. K413 acetylation of mitochondrial mIDH2 is achieved through a series of hierarchical phosphorylation events, optimizing the leukemogenic ability of mIDH2 in AML cells.
Review
Oncology
Georgios Solomou, Alina Finch, Asim Asghar, Chiara Bardella
Summary: Altered metabolism is observed in many cancers, including gliomas, due to mutations in metabolic genes like isocitrate dehydrogenase (IDH). Mutant IDH converts α-ketoglutarate (α-KG) to D2-hydroxyglutarate (D2-HG) instead of isocitrate. Accumulation of D2-HG in IDH mutant tumors has led to the development of small inhibitors to target mutant IDH. This review summarizes the cellular and molecular consequences of IDH mutations and therapeutic approaches for IDH mutant tumors, with a focus on gliomas.
Article
Oncology
Antje Wick, Oliver Baehr, Martin Schuler, Kristoffer Rohrberg, Sant P. Chawla, Filip Janku, David Schiff, Volker Heinemann, Yoshitaka Narita, Heinz-Josef Lenz, Masafumi Ikeda, Yuichi Ando, Wolfgang Wick, Joachim P. Steinbach, Michael C. Burger, Katharina Wenger, Ulrik Lassen, Kamalesh K. Sankhala, Cristiana Roggia, Isabelle Genvresse, Catya Munhoz, Christine Rentzsch, Susanne Reschke, Simon Langer, Markus Wagner, Stefan Kaulfuss, Charles Cai, Eleni Lagkadinou, Michael Jeffers, Carol Pena, Ghazaleh Tabatabai
Summary: BAY1436032, an inhibitor of mIDH1 mutation, showed good tolerability and target inhibition in patients with solid tumors, particularly demonstrating durable objective responses in a subset of patients with LGG.
CLINICAL CANCER RESEARCH
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Xiefeng Yang, Chengcong Hu, Zhen Xing, Yu Lin, Yan Su, Xingfu Wang, Dairong Cao
Summary: This study aimed to evaluate the predictive value of mMRI, SWI, DWI, and DSC-PWI for Ki-67 LI and ATRX mutation status in IDH-mut astrocytoma. The results showed that these imaging modalities could accurately predict Ki-67 LI and ATRX mutation, with a possible improvement in diagnostic performance by combining mMRI and SWI.
EUROPEAN RADIOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Mingxiao Li, Xiaohui Ren, Xuzhu Chen, Jincheng Wang, Shaoping Shen, Haihui Jiang, Chuanwei Yang, Xuzhe Zhao, Qinghui Zhu, Yong Cui, Song Lin
Summary: This study aimed to diagnose IDHmut-Noncodel astrocytoma from other subtypes of gliomas using preoperative MRI and CT. The results showed that the hyperFLAIRrim sign was a specific and sensitive marker for diagnosing this subtype of astrocytoma.
EUROPEAN RADIOLOGY
(2022)
Review
Oncology
Diana D. Shi, Soummitra Anand, Kalil G. Abdullah, Samuel K. McBrayer
Summary: This article summarizes the current understanding of how IDH mutations influence DNA damage in glioma and discusses the clinical implications of these findings.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Wangqi Tian, Weitong Zhang, Yifan Wang, Ruyi Jin, Yuwei Wang, Hui Guo, Yuping Tang, Xiaojun Yao
Summary: IDH is a key metabolic enzyme that is mutated in various tumors, with IDH1 mutations being more frequent than IDH2 mutations. IDH1 mutations lead to accumulation of 2-HG, which impairs cell differentiation. Small molecule inhibitors targeting mutant IDH1 have emerged as a promising therapeutic approach.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Julie J. Miller, L. Nicolas Gonzalez Castro, Samuel McBrayer, Michael Weller, Timothy Cloughesy, Jana Portnow, Ovidiu Andronesi, Jill S. Barnholtz-Sloan, Brigitta G. Baumert, Mitchell S. Berger, Wenya Linda Bi, Ranjit Bindra, Daniel P. Cahill, Susan M. Chang, Joseph F. Costello, Craig Horbinski, Raymond Y. Huang, Robert B. Jenkins, Keith L. Ligon, Ingo K. Mellinghoff, L. Burt Nabors, Michael Platten, David A. Reardon, Diana D. Shi, David Schiff, Wolfgang Wick, Hai Yan, Andreas von Deimling, Martin van den Bent, William G. Kaelin, Patrick Y. Wen
Summary: This article discusses the diagnosis and management of IDH-mutant gliomas, as well as new treatment methods and future research directions.
Article
Oncology
Haoyu Wang, Shuxin Zhang, Xiang Xing, Qiang Yue, Wentao Feng, Siliang Chen, Jun Zhang, Dan Xie, Ni Chen, Yanhui Liu
Summary: Radiomic features of IDHmut pTERTmut gliomas were analyzed using multimodal MRI and a precise diagnostic model was established to identify this type of glioma.
Article
Gastroenterology & Hepatology
Lynda Corrigan, Maeve Lowery
Summary: Cholangiocarcinomas (CCAs) have poor survival outcomes with limited treatment options. Ivosidenib, a selective inhibitor of mutant IDH1, presents a promising treatment option for patients with IDH1 mutant CCA. Future studies may explore the use of this targeted agent in combination with other anticancer treatments to improve survival outcomes in advanced CCA.
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Bin Fan, Yue Chen, Feng Yin, Lei Hua, Caroline Almon, Salah Nabhan, Michael Cooper, Hua Yang, Mohammad Hossain
Summary: In this study, the pharmacokinetics, pharmacodynamics, and PK/PD relationships of ivosidenib and enasidenib in newly diagnosed nnIDH1/2 AML patients were characterized. The results showed that the profiles of ivosidenib and enasidenib in combination with intensive chemotherapy were similar to those when they are given as single agents. These findings support the dosing of ivosidenib or enasidenib in combination with intensive chemotherapy for the treatment of newly diagnosed mIDH1/2 AML patients.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2022)
Article
Oncology
Ruichao Chai, Guanzhang Li, Yuqing Liu, Kenan Zhang, Zheng Zhao, Fan Wu, Yuzhou Chang, Bo Pang, Jingjun Li, Yangfang Li, Tao Jiang, Yongzhi Wang
Summary: The study investigated the role of MGMT promoter methylation in IDH-mutant glioblastoma, finding it to have predictive value with a cutoff value higher than that for IDH-wildtype glioblastoma.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Oncology
Nils Ludwig, Aparna Rao, Poorva Sandlesh, Saigopalakrishna S. Yerneni, Alexander D. Swain, Kristin M. Bullock, Kim M. Hansen, Xiaoran Zhang, Emade Jaman, Jordan Allen, Katharine Krueger, Chang-Sook Hong, William A. Banks, Theresa L. Whiteside, Nduka M. Amankulor
Summary: This study reveals the role of tumor-derived glioma small extracellular vesicles (TEX) in immunomodulation in IDH mutant gliomas. The findings demonstrate that mutIDH TEX are more immunosuppressive compared to wtIDH TEX. Injection of mutIDH TEX reduces tumor-infiltrating immune cells and increases circulating monocytes, even accelerating tumor growth and mortality.
Article
Oncology
Laiz Laura de Godoy, Kheng Choon Lim, Archith Rajan, Gaurav Verma, Mauro Hanaoka, Donald M. O'Rourke, John Y. K. Lee, Arati Desai, Sanjeev Chawla, Suyash Mohan
Summary: The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (H-1-MRS) in identifying IDH-mutant gliomas. The study found that the detection of 2HG and its complex interaction with other metabolites can accurately identify IDH-mutant gliomas.
Article
Pharmacology & Pharmacy
Zhiqiang Wang, Zhibo Zhang, Yong Li, Li Sun, Dezhen Peng, Danyu Du, Xian Zhang, Luwei Han, Liwen Zhao, Ligong Lu, Hongzhi Du, Shengtao Yuan, Meixiao Zhan
Summary: SH1573 is a novel mIDH2 inhibitor with strong selective inhibition of the R140Q protein, promoting differentiation of AML cells. The drug has good pharmacokinetic and toxicological data, making it effective and safe for treating mIDH2 R140Q acute myeloid leukaemia.
ACTA PHARMACEUTICA SINICA B
(2021)
