Idh1-KO Mouse

Idh1, or isocitrate dehydrogenase 1, is a key metabolic enzyme in the tricarboxylic acid (TCA) cycle. It catalyzes the oxidative decarboxylation of isocitrate to α -ketoglutarate (α -KG) and generates NADPH, playing a crucial role in cellular respiration [1,5,6]. Changes in its expression levels or gene mutations may affect enzyme activity and the body's detoxification mechanism [6].

Mutations in Idh1 have been observed in several tumors, such as glioma, acute myeloid leukemia, and chondrosarcoma [1,2,5,7,8,9]. Mutant Idh1 increases the conversion of α -KG to 2 -hydroxyglutarate (2 -HG), leading to epigenetic dysregulation, altered gene expression, and impaired cell differentiation [1,2,5,9]. Small-molecule inhibitors targeting mutant Idh1 (mIdh1) are emerging as a therapeutic approach, with ivosidenib being the first approved for IDH1-mutated AML [1,4]. Also, scutellarin, a natural small molecule, can activate Idh1 to exert antitumor effects in hepatocellular carcinoma [3].

In conclusion, Idh1 is essential for cellular metabolism, especially in the TCA cycle. Its mutations are closely associated with tumorigenesis, mainly through the production of oncometabolite 2 -HG. Research on Idh1, especially regarding its mutant forms, has significant implications for cancer therapy, providing new targets and strategies for treating related malignancies [1-10].

References:

1. Tian, Wangqi, Zhang, Weitong, Wang, Yifan, Tang, Yuping, Yao, Xiaojun. 2022. Recent advances of IDH1 mutant inhibitor in cancer therapy. In Frontiers in pharmacology, 13, 982424. doi:10.3389/fphar.2022.982424. https://pubmed.ncbi.nlm.nih.gov/36091829/

2. Molenaar, Remco J, Wilmink, Johanna W. . IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy. In The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 70, 83-97. doi:10.1369/00221554211062499. https://pubmed.ncbi.nlm.nih.gov/34967233/

3. Cui, Zhao, Li, Caifeng, Liu, Wei, Yang, Hongjun, Chen, Peng. 2024. Scutellarin activates IDH1 to exert antitumor effects in hepatocellular carcinoma progression. In Cell death & disease, 15, 267. doi:10.1038/s41419-024-06625-6. https://pubmed.ncbi.nlm.nih.gov/38622131/

4. Megías-Vericat, Juan Eduardo, Ballesta-López, Octavio, Barragán, Eva, Montesinos, Pau. 2019. IDH1-mutated relapsed or refractory AML: current challenges and future prospects. In Blood and lymphatic cancer : targets and therapy, 9, 19-32. doi:10.2147/BLCTT.S177913. https://pubmed.ncbi.nlm.nih.gov/31413655/

5. Bruce-Brand, Cassandra, Govender, Dhirendra. 2020. Gene of the month: IDH1. In Journal of clinical pathology, 73, 611-615. doi:10.1136/jclinpath-2020-206813. https://pubmed.ncbi.nlm.nih.gov/32727816/

6. Ni, Yingqian, Shen, Peibo, Wang, Xingchen, Luo, Huiyuan, Han, Xiuzhen. 2023. The roles of IDH1 in tumor metabolism and immunity. In Future oncology (London, England), 18, 3941-3953. doi:10.2217/fon-2022-0583. https://pubmed.ncbi.nlm.nih.gov/36621781/

7. Arita, Hideyuki, Narita, Yoshitaka, Yoshida, Akihiko, Yoshimine, Toshiki, Ichimura, Koichi. 2014. IDH1/2 mutation detection in gliomas. In Brain tumor pathology, 32, 79-89. doi:10.1007/s10014-014-0197-x. https://pubmed.ncbi.nlm.nih.gov/25008158/

8. Huang, L Eric. . Friend or foe-IDH1 mutations in glioma 10 years on. In Carcinogenesis, 40, 1299-1307. doi:10.1093/carcin/bgz134. https://pubmed.ncbi.nlm.nih.gov/31504231/

9. Mondesir, Johanna, Willekens, Christophe, Touat, Mehdi, de Botton, Stéphane. 2016. IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives. In Journal of blood medicine, 7, 171-80. doi:10.2147/JBM.S70716. https://pubmed.ncbi.nlm.nih.gov/27621679/