Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex – Pharmacological Treatment using mTOR Inhibitors
Authors:
K. Zitterbart
Authors‘ workplace:
Klinika dětské onkologie LF MU a FN BrnoÚstav experimentální biologie, PřF MU, BrnoRegionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in:
Klin Onkol 2014; 27(6): 401-405
Category:
Review
doi:
https://doi.org/10.14735/amko2014401
Overview
Tuberous sclerosis complex is a neurocutaneous syndrome that results from a germline mutation in TSC1 or TSC2 genes. The pathogenic activation of mTORC1 leads to the development of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex. Blocking of the dysregulated pathway with mTOR inhibitors has the potential to reduce the volume of this low‑ grade brain tumor. This article reviews the current knowledge on the pharmacological treatment of subependymal giant cell astrocytomas. A long‑term follow‑up and early therapeutic intervention should lead to mortality and morbidity reduction and quality of life improvement in patients with tuberous sclerosis complex associated tumors.
Key words:
subependymal giant cell astrocytoma − tuberous sclerosis complex – mTOR – everolimus
This study was supported by the European Regional Development Fund as well as by the State Budget of the Czech Republic: project RECAMO CZ.1.05/2.1.00/03.0101 and the project CEB CZ.1.07/2.3.00/20.0183.
The author has received honoraria from Novartis for the lecture with the article-related topic.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Submitted:
18. 11. 2014
Accepted:
20. 11. 2014
Sources
1. Lagos JC, Gomez MR. Tuberous sclerosis: reappraisal of a clinical entity. Mayo Clin Proc 1967; 42(1):26– 49.
2. Kwiatkowski DJ, Whittemore VH, Thiele EA (ed.). Tuberous sclerosis complex: genes, clinical features and therapeutics. Weinheim: Wiley‑ VCH 2010.
3. Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49(4): 243– 254. doi: 10.1016/ j.pediatrneurol.2013.08.001.
4. Vrtěl R, Filipová H, Vodička R et al. Tuberózní skleróza. Klin Onkol 2009; 22 (Suppl): S50– S53.
5. Petrák B, Gabera A, Filipová H et al. Tuberózní skleróza u dětí sledovaných od novorozeneckého věku pro prenatální nález rhabdomyomů srdce – dvě kazuistiky. Cesk Slov Neurol N 2013; 76/ 109(6): 763– 768.
6. Doležel Z, Ráčilová Z, Pavlovská D et al. Tuberózní skleróza. Pediatr Prax 2012; 13: 130.
7. Zitterbart K. mTOR inhibice: nové možnosti farmakologické léčby nádorů u pacientů s tuberózní sklerózou. Postgrad Med 2014; 16: 880– 886.
8. Gusman M, Servaes S, Feygin T et al. Multimodal imaging in the prenatal diagnosis of tuberous sclerosis complex. Case Rep Pediatr 2012; 2012: 925646. doi: 10.1155/ 2012/ 925646.
9. Kotulska K, Chmielewski D, Borkowska J et al. Long‑term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex. Eur J Paediatr Neurol 2013; 17(5): 479– 485. doi: 10.1016/ j.ejpn.2013.03.002.
10. Hallett L, Foster T, Liu Z et al. Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. Curr Med Res Opin 2011; 27(8): 1571– 1583. doi: 10.1185/ 03007995. 2011.586687.
11. Bissler JJ, Kingswood JC, Radzikowska E et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST‑2): a multicentre, randomised, double‑blind, placebo‑ controlled trial. Lancet 2013; 381(9869): 817– 824.
12. Bissler JJ, McCormack FX, Young LR et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008; 358(2): 140– 151. doi: 10.1056/ NEJMoa063564.
13. Ürge T, Hora M, Hes O et al. Renální angiomyolipom, histologie, diagnostika a terapie. Urol Prax 2005; 6: 270– 272.
14. Webb DW, Kabala J, Osborne JP. A population study of renal disease in patients with tuberous sclerosis. Br J Urol 1994; 74(2): 151– 154.
15. Schillinger F, Montagnac R. Chronic renal failure and its treatment in tuberous sclerosis. Nephrol Dial Transplant 1996; 11(3): 481– 485.
16. Chatziioannou A, Gargas D, Malagari K et al. Transcatheter arterial embolization as therapy of renal angiomyolipomas: the evolution in 15 years of experience. Eur J Radiol 2012; 81(9): 2308– 2312. doi: 10.1016/ j.ejrad.2011.06.003.
17. McCormack FX, Travis WD et al. Lymphangioleiomyomatosis: calling it what it is: a low‑ grade, destructive, metastasizing neoplasm. Am J Respir Crit Care Med 2012; 186(12): 1210– 1212. doi: 10.1164/ rccm.201205‑ 0848OE.
18. McMaster ML, Goldstein AM, Parry DM. Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population. J Med Genet 2011; 48(7): 444– 449. doi: 10.1136/ jmg.2010.085092.
19. Chan JA, Zhang H, Roberts PS et al. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 2004; 63(12): 1236– 1242.
20. Svajdler M Jr, Deák L, Rychlý B et al. Subependymal giant cell astrocytoma with atypical clinical and pathological features: a diagnostic pitfall. Cesk Patol 2013; 49(2): 76– 79.
21. Jóźwiak S, Nabbout R, Curatolo P. Management of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): clinical recommendations. Eur J Paediatr Neurol 2013; 17(4): 348– 352. doi: 10.1016/ j.ejpn.2012.12.008.
22. Roth J, Roach ES, Bartels U et al. Subependymal giant cell astrocytoma: diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol 2013; 49(6): 439– 444. doi: 10.1016/ j.pediatrneurol.2013.08.017.
23. Harter DH, Bassani L, Rodgers SD et al. A management strategy for intraventricular subependymal giant cell astrocytomas in tuberous sclerosis complex. J Neurosurg Pediatr 2014; 13(1): 21– 28. doi: 10.3171/ 2013.9.PEDS13193.
24. Matsumura H, Takimoto H, Shimada N et al. Glioblastoma following radiotherapy in a patient with tuberous sclerosis. Neurol Med Chir (Tokyo) 1998; 38(5): 287– 291.
25. de Ribaupierre S, Dorfmüller G, Bulteau C et al. Subependymal giant‑ cell astrocytomas in pediatric tuberous sclerosis disease: when should we operate? Neurosurgery 2007; 60(1): 83– 89.
26. Sun P, Krueger D, Liu J et al. Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in SEGA‑related conditions: a US national claims database study. Curr Med Res Opin 2012; 28(4): 651– 666. doi: 10.1185/ 03007995.2012.658908.
27. Krueger DA, Care MM, Holland K et al. Everolimus for subependymal giant‑ cell astrocytomas in tuberous sclerosis. N Engl J Med 2010; 363(19): 1801– 1811. doi: 10.1056/ NEJMoa1001671.
28. Franz DN, Belousova E, Sparagana S et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST‑1): a multicentre, randomised, placebo‑ controlled phase 3 trial. Lancet 2013; 381(9861): 125– 132. doi: 10.1016/ S0140‑ 6736(12)61134‑ 9.
29. Franz DN. Everolimus: an mTOR inhibitor for the treatment of tuberous sclerosis. Expert Rev Anticancer Ther 2011; 11(8): 1181– 1192. doi: 10.1586/ era.11.93.
30. Howell JJ, Ricoult SJ, Ben‑ Sahra I et al. A growing role for mTOR in promoting anabolic metabolism. Biochem Soc Trans 2013; 41(4): 906– 912. doi: 10.1042/ BST20130041.
31. Serkova N, Jacobsen W, Niemann CU et al. Sirolimus, but not the structurally related RAD (everolimus), enhances the negative effects of cyclosporine on mitochondrial metabolism in the rat brain. Br J Pharmacol 2001; 133(6): 875– 885.
32. Študentová H, Melichar B. Nový mechanizmus v léčbě karcinomu ledviny: m‑ TOR – nová cílová struktura. Onkologie 2010; 4(3): 185– 188.
33. Franz DN, Leonard J, Tudor C et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 2006; 59(3): 490– 498.
34. Lam C, Bouffet E, Tabori U et al. Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous system tumors. Pediatr Blood Cancer 2010; 54(3): 476– 479. doi: 10.1002/ pbc.22298.
35. Campen CJ, Porter BE. Subependymal giant cell astrocytoma (SEGA) treatment update. Curr Treat Options Neurol 2011; 13(4): 380– 385. doi: 10.1007/ s11940‑ 011‑ 0123‑ z.
36. Franz DN. 11th European Congress on Epileptology; June 29– July 3, 2014; Stockholm, Sweden.
37. Franz DN. 13th International Child Neurology Congress; May 2014, Brazil.
38. European Medicines Agency [homepage on the Internet]. Available from: http:/ / www.ema.europa.eu/ docs/ en_GB/ document_library/ EPAR_– _Product_Information/ human/ 002311/ WC500112238.pdf.
39. Grünwald V, Weikert S, Pavel ME et al. Practical management of everolimus‑related toxicities in patients with advanced solid tumors. Onkologie 2013; 36: 295– 302.
40. Peterson ME. Management of adverse events in patients with hormonereceptor‑ positive breast cancer treated with everolimus: observations from a phase III clinical trial. Support Care Cancer 2013; 21(8): 2341– 2349. doi: 10.1007/ s00520‑ 013‑ 1826‑ 3.
41. Boobes Y, Bernieh B, Saadi H et al. Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus. Int Urol Nephrol 2010; 42(2): 493– 498. doi: 10.1007/ s11255‑ 009‑ 9644‑ 8.
42. Wheless JW, Klimo P Jr. Subependymal giant cell astrocytomas in patients with tuberous sclerosis complex: considerations for surgical or pharmacotherapeutic intervention. J Child Neurol 2014; 29(11): 1562– 1571. doi: 10.1177/ 0883073813501870.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2014 Issue 6
Most read in this issue
- Adverse Effects of Modern Treatment of Malignant Melanoma and their Treatment/ Management
- Cancer Incidence and Mortality in the Czech Republic
- Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex – Pharmacological Treatment using mTOR Inhibitors
- Squamous Cell Carcinoma in Localized Scleroderma