Theoretical and Natural Science

- The Open Access Proceedings Series for Conferences

Theoretical and Natural Science

Vol. 6, 03 August 2023

Open Access | Article

Mutated isocitrate dehydrogenase and therapeutic modalities

Kaijia Chen * 1
1 Bancroft School

* Author to whom correspondence should be addressed.

Theoretical and Natural Science, Vol. 6, 252-258
Published 03 August 2023. © 2023 The Author(s). Published by EWA Publishing
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation Kaijia Chen. Mutated isocitrate dehydrogenase and therapeutic modalities. TNS (2023) Vol. 6: 252-258. DOI: 10.54254/2753-8818/6/20230245.


Isocitrate dehydrogenase (IDH) is crucial in the metabolism pathway that converts isocitrate to α-ketoglutarate. When isocitrate dehydrogenase is mutated, IDH produces 2-hydroxyglutarate instead of alpha-ketoglutarate. The newly formed IDH, with the ability to dysregulate the metabolic pathways of cells, can potentially lead to the development of cancer. The mutation leads to malignancies such as acute myeloid leukemia and glioma. Current treatment for IDH-related malignancies includes IDH inhibitors, epigenetic modulators, immunotherapies, and cancer vaccination. The development of a cancer vaccine requires the discovery of a suitable epitope being found. Newly developed deep learning algorithms have the ability to predict protein structures and thus have the potential to help discover suitable epitopes for cancer vaccines. This study discusses the structure of IDH and gives an overview of how mutated IDH can potentially cause malignancies. In addition, this study proposed potential approaches with deep learning to aid the investigation of preventing IDH using cancer vaccines.


isocitrate dehydrogenase, acute myeloid leukemia, glioma, deep learning, cancer vaccine


1. Pelcovits, A., & Niroula, R. (2020). Acute Myeloid Leukemia: A Review. Rhode Island medical journal (2013), 103(3), 38–40.

2. Xu, Can et al. “Origin, activation, and targeted therapy of glioma-associated macrophages.” Frontiers in immunology vol. 13 974996. 6 Oct. 2022

3. Han, S., Liu, Y., Cai, S. J., Qian, M., Ding, J., Larion, M., Gilbert, M. R., & Yang, C. (2020). IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. British journal of cancer, 122(11), 1580–1589.

4. Goethe, E., Carter, B. Z., Rao, G., & Pemmaraju, N. (2018). Glioblastoma and acute myeloid leukemia: malignancies with striking similarities. Journal of neuro-oncology, 136(2), 223–231.

5. Wang, Zeyu et al. “Circadian clock genes promote glioma progression by affecting tumour immune infiltration and tumour cell proliferation.” Cell proliferation vol. 54,3 (2021): e12988. doi:10.1111/cpr.12988

6. Schumacher, T., Bunse, L., Pusch, S., Sahm, F., Wiestler, B., Quandt, J., Menn, O., Osswald, M., Oezen, I., Ott, M., Keil, M., Balß, J., Rauschenbach, K., Grabowska, A. K., Vogler, I., Diekmann, J., Trautwein, N., Eichmüller, S. B., Okun, J., Stevanović, S., … Platten, M. (2014). A vaccine targeting mutant IDH1 induces antitumour immunity. Nature, 512(7514), 324–327.

7. Cadoux-Hudson, T., Schofield, C. J., & McCullagh, J. S. O. (2021). Isocitrate dehydrogenase gene variants in cancer and their clinical significance. Biochemical Society transactions, 49(6), 2561–2572.

8. Reitman, Z. J., & Yan, H. (2010). Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. Journal of the National Cancer Institute, 102(13), 932–941.

9. Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., Fulton, L. A., Locke, D. P., Magrini, V. J., Abbott, R. M., Vickery, T. L., Reed, J. S., Robinson, J. S., Wylie, T., Smith, S. M., Carmichael, L., … Ley, T. J. (2009). Recurring mutations found by sequencing an acute myeloid leukemia genome. The New England journal of medicine, 361(11), 1058–1066.

10. Fujii, T., Khawaja, M. R., DiNardo, C. D., Atkins, J. T., & Janku, F. (2016). Targeting isocitrate dehydrogenase (IDH) in cancer. Discovery medicine, 21(117), 373–380.

11. Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., Friedman, H., Friedman, A., Reardon, D., Herndon, J., Kinzler, K. W., Velculescu, V. E., Vogelstein, B., & Bigner, D. D. (2009). IDH1 and IDH2 mutations in gliomas. The New England journal of medicine, 360(8), 765–773.

12. Testa, U., Castelli, G., & Pelosi, E. (2020). Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias. Cancers, 12(9), 2427.

13. Kernytsky, A., Wang, F., Hansen, E., Schalm, S., Straley, K., Gliser, C., Yang, H., Travins, J., Murray, S., Dorsch, M., Agresta, S., Schenkein, D. P., Biller, S. A., Su, S. M., Liu, W., & Yen, K. E. (2015). IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition. Blood, 125(2), 296–303.

14. Rohle, D., Popovici-Muller, J., Palaskas, N., Turcan, S., Grommes, C., Campos, C., Tsoi, J., Clark, O., Oldrini, B., Komisopoulou, E., Kunii, K., Pedraza, A., Schalm, S., Silverman, L., Miller, A., Wang, F., Yang, H., Chen, Y., Kernytsky, A., Rosenblum, M. K., … Mellinghoff, I. K. (2013). An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science (New York, N.Y.), 340(6132), 626–630.

15. Flavahan, W. A., Drier, Y., Liau, B. B., Gillespie, S. M., Venteicher, A. S., Stemmer-Rachamimov, A. O., Suvà, M. L., & Bernstein, B. E. (2016). Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature, 529(7584), 110–114.

16. Cao, X., Lu, Y., Liu, Y., Zhou, Y., Song, H., Zhang, W., Davis, D., Cui, J., Hao, S., Jung, J., Wu, Q., Park, D. M., & Yang, C. (2019). Combination of PARP inhibitor and temozolomide to suppress chordoma progression. Journal of molecular medicine (Berlin, Germany), 97(8), 1183–1193.

17. Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., He, T., Shi, X., Gerszten, R. E., Zhang, Y., Yeh, J. J., Curry, W. T., Zhao, D., Sundaram, S., Nigim, F., Koerner, M. V. A., … Cahill, D. P. (2015). Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion. Cancer cell, 28(6), 773–784.

18. Reczek CR, Chandel NS. The two faces of reactive oxygen species in cancer. Annu. Rev. Cancer Biol. 2017;1 1:79–98.

19. Bunse, L., Pusch, S., Bunse, T., Sahm, F., Sanghvi, K., Friedrich, M., Alansary, D., Sonner, J. K., Green, E., Deumelandt, K., Kilian, M., Neftel, C., Uhlig, S., Kessler, T., von Landenberg, A., Berghoff, A. S., Marsh, K., Steadman, M., Zhu, D., Nicolay, B., … Platten, M. (2018). Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nature medicine, 24(8), 1192–1203.

20. Medeiros, B. C., Fathi, A. T., DiNardo, C. D., Pollyea, D. A., Chan, S. M., & Swords, R. (2017). Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia, 31(2), 272–281.

21. Fan B, Le K, Manyak E, Liu H, Prahl M, Bowden C et al. Longitudinal pharmacokinetic/pharmacodynamic profile of AG-120, a potent inhibitor of the IDH1 mutant protein, in a phase 1 study of IDH1-mutant advanced hematologic malignancies. Blood 2015; 126: Abstract 1310.

22. Morse, M. A., Gwin, W. R., 3rd, & Mitchell, D. A. (2021). Vaccine Therapies for Cancer: Then and Now. Targeted oncology, 16(2), 121–152.

23. Luu, A. M., Leistico, J. R., Miller, T., Kim, S., & Song, J. S. (2021). Predicting TCR-Epitope Binding Specificity Using Deep Metric Learning and Multimodal Learning. Genes, 12(4), 572.

24. Choi, Y. S., Bae, S., Chang, J. H., Kang, S. G., Kim, S. H., Kim, J., Rim, T. H., Choi, S. H., Jain, R., & Lee, S. K. (2021). Fully automated hybrid approach to predict the IDH mutation status of gliomas via deep learning and radiomics. Neuro-oncology, 23(2), 304–313.

25. Nguyen, H. D., Allaire, A., Diamandis, P., Bisaillon, M., Scott, M. S., & Richer, M. (2020). A machine learning analysis of a "normal-like" IDH-WT diffuse glioma transcriptomic subgroup associated with prolonged survival reveals novel immune and neurotransmitter-related actionable targets. BMC medicine, 18(1), 280.

26. Yan, J., Zhao, Y., Chen, Y., Wang, W., Duan, W., Wang, L., Zhang, S., Ding, T., Liu, L., Sun, Q., Pei, D., Zhan, Y., Zhao, H., Sun, T., Sun, C., Wang, W., Liu, Z., Hong, X., Wang, X., Guo, Y., … Zhang, Z. (2021). Deep learning features from diffusion tensor imaging improve glioma stratification and identify risk groups with distinct molecular pathway activities. EBioMedicine, 72, 103583.

27. Jumper, John et al. “Highly accurate protein structure prediction with AlphaFold.” Nature vol. 596,7873 (2021): 583-589.

Data Availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:

1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.

3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).

Volume Title
Proceedings of the International Conference on Modern Medicine and Global Health (ICMMGH 2023)
ISBN (Print)
ISBN (Online)
Published Date
03 August 2023
Theoretical and Natural Science
ISSN (Print)
ISSN (Online)
03 August 2023
Open Access
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Copyright © 2023 EWA Publishing. Unless Otherwise Stated