Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex
| العنوان: | Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex |
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| المؤلفون: | Darcy A. Krueger, Jeffrey P. MacKeigan |
| المصدر: | Neuro-Oncology. 17:1550-1559 |
| بيانات النشر: | Oxford University Press (OUP), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Pathology, medicine.medical_specialty, Antineoplastic Agents, Review, Biology, Tuberous Sclerosis Complex 1 Protein, Tuberous sclerosis, Tuberous Sclerosis, Tuberous Sclerosis Complex 2 Protein, medicine, Animals, Humans, Everolimus, PI3K/AKT/mTOR pathway, Sirolimus, Clinical Trials as Topic, Antibiotics, Antineoplastic, Brain Neoplasms, Cell growth, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins, medicine.disease, nervous system diseases, Treatment Outcome, medicine.anatomical_structure, Oncology, Glioma, Subependymal, Cancer research, Female, Neurology (clinical), TSC1, TSC2, Signal Transduction, medicine.drug |
| الوصف: | Tuberous sclerosis complex (TSC) is a genetic autosomal dominant disorder characterized by benign tumor-like lesions, called hamartomas, in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These hamartomas cause a diverse set of clinical problems based on their location and often result in epilepsy, learning difficulties, and behavioral problems. TSC is caused by mutations within the TSC1 or TSC2 genes that inactivate the genes' tumor-suppressive function and drive hamartomatous cell growth. In normal cells, TSC1 and TSC2 integrate growth signals and nutrient inputs to downregulate signaling to mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine kinase that controls cell growth and cell survival. The molecular connection between TSC and mTOR led to the clinical use of allosteric mTOR inhibitors (sirolimus and everolimus) for the treatment of TSC. Everolimus is approved for subependymal giant cell astrocytomas and renal angiomyolipomas in patients with TSC. Sirolimus, though not approved for TSC, has undergone considerable investigation to treat various aspects of the disease. Everolimus and sirolimus selectively inhibit mTOR signaling with similar molecular mechanisms, but with distinct clinical profiles. This review differentiates mTOR inhibitors in TSC while describing the molecular mechanisms, pathogenic mutations, and clinical trial outcomes for managing TSC. |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::222dfd22b1d0309700fe32bfed76040aTest https://doi.org/10.1093/neuonc/nov152Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....222dfd22b1d0309700fe32bfed76040a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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