title: Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?
abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant and multi-system genetic disorder in humans. TSC affects around 25,000 to 40,000 individuals in the United States and about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns. TSC occurs in all races and ethnic groups, and in both genders. TSC is caused by defects or mutations in two genes, TSC1 and TSC2. Loss of TSC1/TSC2 leads to dysregulation of mTOR, resulting in aberrant cell differentiation and development, and abnormal enlargement of cells. TSC is characterized by the development of benign and/or malignant tumors in several organs including renal/liver angiomyolipomas, facial angiofibroma, lymphangiomyomatosis, cardiac rhabdomyomas, retinal astrocytic, renal cell carcinoma, and brain subependymal giant cell astrocytomas (SEGA). In addition, TSC disease causes disabling neurologic disorders, including epilepsy, mental retardation and autism. Particularly problematic are the development of renal angiomyolipomas, which tend to be larger, bilateral, multifocal and present at a younger age compared with sporadic forms. In addition, SEGA block the flow of fluid within the brain, causing a buildup of fluid and pressure that leads to blurred vision and seizures. In the current review, we describe the pathology of TSC disease in key organs and summarize the use of mTOR inhibitors to treat tumors in TSC patients.
authors.affiliation: Geriatric Research Education and Clinical Center, South Texas, Veterans Healthcare System; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Samy L
authors.initials: SL
authors.lastname: Habib
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Noor Y
authors.initials: NY
authors.lastname: Al-Obaidi
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Nowacki
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pietkun
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zegarska
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kloskowski
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zegarski
authors.affiliation: Collegium Medicum, Bydgoszcz and Nicolaus Copernicus University, Torun, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Drewa
authors.affiliation: Department of Pathology.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Medina
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Zhenze
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Sitai
authors.initials: S
authors.lastname: Liang
keywords: AML; LAM; SEGA.; TSC; mTOR inhibitors