Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs

<b>Background/Objectives</b>: Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disorder caused by mutations in the <i>TSC1</i> and <i>TSC2</i> genes, which disrupt the regulation of the mammalian target of rapamycin (mTOR) pathway, a critical...

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Main Authors: Aurora Alexandra Jurca, Alexandru Daniel Jurca, Codruta Diana Petchesi, Dan Bembea, Claudia Maria Jurca, Emilia Severin, Sanziana Jurca, Cosmin Mihai Vesa
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/3/368
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author Aurora Alexandra Jurca
Alexandru Daniel Jurca
Codruta Diana Petchesi
Dan Bembea
Claudia Maria Jurca
Emilia Severin
Sanziana Jurca
Cosmin Mihai Vesa
author_facet Aurora Alexandra Jurca
Alexandru Daniel Jurca
Codruta Diana Petchesi
Dan Bembea
Claudia Maria Jurca
Emilia Severin
Sanziana Jurca
Cosmin Mihai Vesa
author_sort Aurora Alexandra Jurca
collection DOAJ
description <b>Background/Objectives</b>: Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disorder caused by mutations in the <i>TSC1</i> and <i>TSC2</i> genes, which disrupt the regulation of the mammalian target of rapamycin (mTOR) pathway, a critical regulator of cellular growth. The disorder presents as a multisystem condition, with benign tumors (hamartomas) developing in organs such as the brain, skin, heart, kidneys, and lungs, leading to significant clinical variability and impact on quality of life. This review aims to summarize recent advances in the understanding of TSC pathogenesis and clinical variability and evaluate the therapeutic breakthroughs in targeted treatments. <b>Methods</b>: A narrative review was conducted using various available databases. We applied objective evaluation metrics, such as the impact factor of the journals and the citation count, to assess the quality of the studies. <b>Results</b>: Targeted therapies, particularly mTOR inhibitors (mTORis), have shown efficacy in reducing hamartoma size, improving neuropsychiatric symptoms, and enhancing patient outcomes. Despite these advances, variability in disease expression poses challenges in diagnosis and individualized management strategies. <b>Conclusions</b>: Challenges such as early diagnosis, optimizing long-term outcomes, and addressing residual unmet needs remain critical. Future research should prioritize precision medicine approaches and patient-centered care models within centers of expertise to improve treatment efficacy and quality of life for individuals with TSC.
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spelling doaj-art-cd4f33dbfed94de798ee03f96013e2292025-08-20T03:43:36ZengMDPI AGLife2075-17292025-02-0115336810.3390/life15030368Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic BreakthroughsAurora Alexandra Jurca0Alexandru Daniel Jurca1Codruta Diana Petchesi2Dan Bembea3Claudia Maria Jurca4Emilia Severin5Sanziana Jurca6Cosmin Mihai Vesa7Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, RomaniaDepartment of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Sq., 410081 Oradea, RomaniaDepartment of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Sq., 410081 Oradea, RomaniaDepartment of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Sq., 410081 Oradea, RomaniaDepartment of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Sq., 410081 Oradea, RomaniaDepartment of Genetics, University of Medicine and Pharmacy “Carol Davila”, Dionisie Lupu Street, Number 37, District 2, 020021 Bucharest, RomaniaFaculty of Medicine and Pharmacy, University of Oradea, December Sq., 410081 Oradea, RomaniaDepartment of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 1 December Sq., 410081 Oradea, Romania<b>Background/Objectives</b>: Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disorder caused by mutations in the <i>TSC1</i> and <i>TSC2</i> genes, which disrupt the regulation of the mammalian target of rapamycin (mTOR) pathway, a critical regulator of cellular growth. The disorder presents as a multisystem condition, with benign tumors (hamartomas) developing in organs such as the brain, skin, heart, kidneys, and lungs, leading to significant clinical variability and impact on quality of life. This review aims to summarize recent advances in the understanding of TSC pathogenesis and clinical variability and evaluate the therapeutic breakthroughs in targeted treatments. <b>Methods</b>: A narrative review was conducted using various available databases. We applied objective evaluation metrics, such as the impact factor of the journals and the citation count, to assess the quality of the studies. <b>Results</b>: Targeted therapies, particularly mTOR inhibitors (mTORis), have shown efficacy in reducing hamartoma size, improving neuropsychiatric symptoms, and enhancing patient outcomes. Despite these advances, variability in disease expression poses challenges in diagnosis and individualized management strategies. <b>Conclusions</b>: Challenges such as early diagnosis, optimizing long-term outcomes, and addressing residual unmet needs remain critical. Future research should prioritize precision medicine approaches and patient-centered care models within centers of expertise to improve treatment efficacy and quality of life for individuals with TSC.https://www.mdpi.com/2075-1729/15/3/368TSC1 geneTSC2 genehamartomasmTOR inhibitors
spellingShingle Aurora Alexandra Jurca
Alexandru Daniel Jurca
Codruta Diana Petchesi
Dan Bembea
Claudia Maria Jurca
Emilia Severin
Sanziana Jurca
Cosmin Mihai Vesa
Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
Life
TSC1 gene
TSC2 gene
hamartomas
mTOR inhibitors
title Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
title_full Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
title_fullStr Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
title_full_unstemmed Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
title_short Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs
title_sort tuberous sclerosis complex new insights into pathogenesis and therapeutic breakthroughs
topic TSC1 gene
TSC2 gene
hamartomas
mTOR inhibitors
url https://www.mdpi.com/2075-1729/15/3/368
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