Thalidomide - a chance for use in modern disease treatment?
DOI:
https://doi.org/10.12775/JEHS.2025.81.59794Keywords
thalidomide, molecular mechanism, teratogenic effect, anti-inflammatory effect, immunomodulation, anti-angiogenesis, treatmentAbstract
Thalidomide, despite its controversial history associated with teratogenic effects is currently used in the treatment of various conditions including oncological, immunological and dermatological diseases. The drug exhibits anti-inflammatory, immunomodulatory and anti-angiogenic effects, making it potentially effective in the treatment of various diseases. The mechanism of action is based on modulating the CRL4CRBN E3 ubiquitin ligase complex by binding to cereblon (CRBN), which leads to a change in the substrates recognized by this complex and the degradation of specific proteins. Thalidomide is used in the treatment of multiple myeloma, especially in cases resistant to other treatment methods. In addition, it can support the treatment of glioblastoma multiforme due to its anti-angiogenic and immunomodulatory effects. It is also used in the treatment of Crohn's disease, systemic lupus erythematosus, and idiopathic pulmonary fibrosis (IPF). In Crohn's disease it works by blocking TNF-α and modulating the immune response. In cutaneous lupus erythematosus it reduces inflammation, modulates the immune response and inhibits angiogenesis. In IPF, it inhibits the production of pro-inflammatory cytokines and reduces oxidative stress. The use of thalidomide is associated with a risk of teratogenicity, which requires strict control and the use of effective methods of contraception. In addition thalidomide can cause side effects, mainly hematological and gastrointestinal disorders. Due to the side effect profile, the use of thalidomide requires caution and close monitoring of the patient by a physician.
References
1. Jung YJ, Tweedie D, Scerba MT, Greig NH. Neuroinflammation as a Factor of Neurodegenerative Disease: Thalidomide Analogs as Treatments. Frontiers in Cell and Developmental Biology. 2019 Dec 4;7.
2. ITO T, HANDA H. Molecular mechanisms of thalidomide and its derivatives. Proceedings of the Japan Academy, Series B. 2020 Jun 11;96(6):189–203.
3. Ren Q, Zhou YL, Wang L, Chen YS, Ma YN, Li PP, et al. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Annals of Hematology. 2018 Oct 22;97(10):1933–9.
4. Lu Y, Wei Z, Yang G, Lai Y, Liu R. Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis. Frontiers in Pharmacology. 2022 Jan 11;12.
5. Bramuzzo M, Giudici F, Arrigo S, Lionetti P, Zuin G, Romano C, et al. Efficacy and Tolerance of Thalidomide in Patients With Very Early Onset Inflammatory Bowel Disease. Inflammatory Bowel Diseases. 2024 Jan 5;30(1):20–8.
6. Keddie S, Bharambe V, Jayakumar A, Shah A, Sanchez V, Adams A, et al. Clinical perspectives into the use of thalidomide for central nervous system tuberculosis. European Journal of Neurology. 2018 Nov 18;25(11):1345–51.
7. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. American Journal of Hematology. 2022 Aug 23;97(8):1086–107.
8. Bobin A, Leleu X. Recent advances in the treatment of multiple myeloma: a brief review. Faculty Reviews. 2022 Sep 29;11.
9. Guedes A, Becker RG, Teixeira LEM. Mieloma Múltiplo (Parte 1) – Atualização Sobre Epidemiologia, Critérios Diagnósticos, Tratamento Sistêmico e Prognóstico. Revista Brasileira de Ortopedia. 2023 Jun 29;58(03):361–7.
10. Li T, Qiu Y, Li X, Zhuang X, Huang S, Li M, et al. Thalidomide Combined With Azathioprine as Induction and Maintenance Therapy for Azathioprine-Refractory Crohn’s Disease Patients. Frontiers in Medicine. 2020 Nov 6;7.
11. Domingo S, Solé C, Moliné T, Ferrer B, Ordi-Ros J, Cortés-Hernández J. Efficacy of Thalidomide in Discoid Lupus Erythematosus: Insights into the Molecular Mechanisms. Dermatology. 2020;236(5):467–76.
12. Hussain K, Patel P, Roberts N. The role of thalidomide in dermatology. Clin Exp Dermatol. 2022 Apr;47(4):667-674. doi: 10.1111/ced.15019. Epub 2021 Dec 19. PMID: 34779533.
13. Dsouza NN, Alampady V, Baby K, Maity S, Byregowda BH, Nayak Y. Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis. Inflammopharmacology. 2023 Jun 25;31(3):1167–82.
14. Chen L, Ni X, Zhang H, Wu M, Liu J, Xu S, et al. Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer. International Journal of Nanomedicine. 2018 Apr;Volume 13:2463–76.
15. Li Y, Shi K, Qi F, Yu Z, Chen C, Pan J, Wu G, Chen Y, Li J, Chen Y, Zhou T, Li X, Xia J. Thalidomide combined with short-term low-dose glucocorticoid therapy for the treatment of severe COVID-19: A case-series study. Int J Infect Dis. 2021 Feb;103:507-513. doi: 10.1016/j.ijid.2020.12.023. Epub 2020 Dec 14. PMID: 33333254; PMCID: PMC7834521.,
16. Eatmann AI, Hamouda E, Hamouda H, Farouk HK, Jobran AWM, Omar AA, et al. Potential Use of Thalidomide in Glioblastoma Treatment: An Updated Brief Overview. Metabolites. 2023 Apr 11;13(4):543.
17. Motamed-Sanaye A, Mortezaei A, Afshari AR, Saadatian Z, Faraji AH, Sheehan JP, et al. Angiogenesis inhibitors effects on overall survival and progression-free survival in newly diagnosed primary glioblastoma multiforme: a meta-analysis of twelve randomized clinical trials. Journal of Neuro-Oncology. 2025 Jan 5;171(2):313–28.
18. Pan J, Dong F, Ma L, Zhao C, Qin F, Wen J, et al. Therapeutic effects of thalidomide on patients with systemic sclerosis-associated interstitial lung disease. Journal of Scleroderma and Related Disorders. 2023 Oct 14;8(3):231–40.
19. Sundaresan L, Giri S, Singh H, Chatterjee S. Repurposing of thalidomide and its derivatives for the treatment of SARS‐coV‐2 infections: Hints on molecular action. British Journal of Clinical Pharmacology. 2021 Oct 15;87(10):3835–50.
20. Combe B. Thalidomide: new indications? Joint Bone Spine. 2001 Dec;68(6):582–7.
21. Vargesson N. The teratogenic effects of thalidomide on limbs. Journal of Hand Surgery (European Volume). 2019 Jan 18;44(1):88–95.
22. Vargesson N. Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Research Part C: Embryo Today: Reviews. 2015 Jun 4;105(2):140–56.
23. Kurkin D v., Bakupin DA, Morkovin EI, Krysanov IS, Makarova E v., Tsaplina AP, et al. Thalidomide: History of Research and Perspectives for Its Medical Use (Review). Pharmaceutical Chemistry Journal. 2024 Oct 13;58(7):1001–10.
24. Ugur MC, Baysal M, Umit EG. The Role of Thalidomide and Its Analogs in the Treatment of Hereditary Hemorrhagic Telangiectasia: A Systematic Review. Journal of Clinical Medicine. 2024 Sep 12;13(18):5404.
25. Dsouza NN, Alampady V, Baby K, Maity S, Byregowda BH, Nayak Y. Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis. Inflammopharmacology. 2023 Jun 25;31(3):1167–82.
26. Peng X, Lin ZW, Zhang M, Yao JY, Zhao JZ, Hu PJ, et al. The efficacy and safety of thalidomide in the treatment of refractory Crohn’s disease in adults: a double-center, double-blind, randomized–controlled trial. Gastroenterology Report. 2022 Jan 25;10.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Marta Turek, Julia Szlążek, Michalina Zagalska, Adam Jan Ząbek, Jakub Paweł Kuźniar, Emilia Gabriela Chrzanowska, Tomasz Tamborski, Adam Grzebinoga, Barbara Roguska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 197
Number of citations: 0
