IDH Mutations in Chondrosarcoma: Case Closed or Not?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Frequency and Prognostic Value of IDH1 and IDH2 Mutations
3. Oncogenic Activities of IDH Mutations
4. Inhibition of the IDHMUT Protein
5. Synthetic Lethal Interactions with the IDH Mutation
6. Putting the IDH Mutation into Context to Define Underlying Vulnerabilities
7. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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AML | Glioma | Cholangiocarcinoma | Chondrosarcoma | |
---|---|---|---|---|
Frequency of IDHMUT | ~10–15% [14] | >70% [14] | ~15–20% [14] | ~50% [7,8,9] |
Most common IDHMUT variant | IDH2 p.R140Q (~40%) Weak D-2-HG Producer [16,17] | IDH1 p.R132H (~90%) Weak D-2-HG Producer [16,18] | IDH1 p.R132C (~60%) Strong D-2-HG Producer [16,18] | IDH1 p.R132C (~60%) Strong D-2-HG Producer [15,16,18] |
IDHMUT inhibition in vitro | Differentiation [26] | No effect [27] | No effect [28] | Controversial [27,29,30,31] |
IDHMUT inhibition clinical trials | ~40% response, secondary resistance [32,33,34,35] | Less promising, prolonged disease control in subset [36] | Less promising, prolonged disease control in subset [37] | Durable disease control in subset [38] |
IDHMUT effect on outcome | No difference (in MDS: worse prognosis) [20,21] | Better prognosis, due to favourable response? [22] | Beneficial? [23] | Controversial [15,24,25] |
AML | Glioma | Cholangiocarcinoma | Chondrosarcoma | |
---|---|---|---|---|
Radiotherapy | Molenaar 2018 [47] * | Li 2013 [48] Kessler 2015 [49] | De Jong 2019 [61] * | |
Temozolomide | Lu 2017 [50] Tateishi 2017 [51] * | Venneker 2019 [66] * | ||
PARP inh. | Sulkowski 2017 [52] Molenaar 2018 [47] * | Sulkowski 2017 [52] | Wang 2020 [53] | Venneker 2019 [66] * Palubeckaitė [67] * |
Bcl-2/Bcl-xL inh. | Chan 2015 [54] | Karpel-Massler 2017 [55] | De Jong 2018 [62] * | |
BET inh. | Chen 2013 [56] | Fujiwara 2018 [28] | Fujiwara 2018 [28] * | |
DNMT inh. | Turcan 2013 [57] * | |||
mTOR inh. | Batsios 2019 [58] | Addie 2019 [63] * | ||
NAMPT inh. | Tateishi 2015 [27] * | Peterse 2017 [64] * | ||
Glutaminolysis inh. | Emadi 2014 [59] * | Seltzer 2010 [60] | Peterse 2018 [65] * |
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Venneker, S.; Bovée, J.V.M.G. IDH Mutations in Chondrosarcoma: Case Closed or Not? Cancers 2023, 15, 3603. https://doi.org/10.3390/cancers15143603
Venneker S, Bovée JVMG. IDH Mutations in Chondrosarcoma: Case Closed or Not? Cancers. 2023; 15(14):3603. https://doi.org/10.3390/cancers15143603
Chicago/Turabian StyleVenneker, Sanne, and Judith V. M. G. Bovée. 2023. "IDH Mutations in Chondrosarcoma: Case Closed or Not?" Cancers 15, no. 14: 3603. https://doi.org/10.3390/cancers15143603
APA StyleVenneker, S., & Bovée, J. V. M. G. (2023). IDH Mutations in Chondrosarcoma: Case Closed or Not? Cancers, 15(14), 3603. https://doi.org/10.3390/cancers15143603