Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex—Current Views on Their Pathogenesis and Management

Abstract

Introduction, Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder caused by mutations inactivating TSC1 or TSC2 genes and characterized by the presence of tumors involving many organs, including the brain, heart, kidneys, and skin. Subependymal giant cell astrocytoma (SEGA) is a slow-growing brain tumor almost exclusively associated with TSC. State of the Art: Despite the fact that SEGAs are benign, they require well-considered decisions regarding the timing and modality of pharmacological or surgical treatment. In TSC children and adolescents, SEGA is the major cause of mortality and morbidity. Clinical Implications: Until recently, surgical resection has been the standard therapy for SEGAs but the discovery of the role of the mTOR pathway and the introduction of mTOR inhibitors to clinical practice changed the therapeutic landscape of these tumors. In the current paper, we discuss the pros and cons of mTOR inhibitors and surgical approaches in SEGA treatment. Future Directions: In 2021, the International Tuberous Sclerosis Complex Consensus Group proposed a new integrative strategy for SEGA management. In the following review, we discuss the proposed recommendations and report the results of the literature search for the latest treatment directions.

Polymorphism of clinical manifestations of orphan diseases in children with ARID1A and ARID1B gene mutations

“…Субепендимальна гігантоклітинна астроцитома -це повільно зростаючі пухлини головного мозку, характерні ознаки яких спостерігаються в 5-10% пацієнтів із комплексом туберозного склерозу, ця знахідка є нетиповою для такого типу пухлин та не описана раніше в літературі при мутаціях гена ARID1А. СЕГА за відсутності мутацій генів, характерних для туберозного склерозу -TSC1 і TSC2, трапляється надзвичайно рідко [4].…”

Vitamin D in tuberous sclerosis complex-associated tumors

“…Notably, vitamin D and its analogs restrict gliomas by inducing cell cycle arrest via multiple mechanisms, including the PI3K/AKT pathway ( 12 ). Importantly, while therapy with mTORi and PI3Kα inhibitor is necessary for GB treatment ( 38 ), activation of the PI3K/AKT ( 39 ) and MAPK/ERK pathways ( 40 ) also plays an important role in SEGA development. Moreover, in TSC, the Raf-1/MAPK/ERK cascade, in addition to mTOR, leads to 4E-binding protein 1 phosphorylation, increased cyclin D protein levels, and increased protein synthesis ( 41 ).…”