Bone and soft tissue sarcomas, tumors of the skinBone and soft tissue sarcomas, tumors of the skinСаркомы костей, мягких тканей и опухоли кожи2219-46142782-3687Publishing House ABV Press57610.17650/2219-4614-2022-14-3-33-41SOFT TISSUE SARCOMASСАРКОМЫ МЯГКИХ ТКАНЕЙClinical and molecular features of neurofibromatosis types 1 and 2: a review of the literatureКлинические и молекулярные особенности нейрофиброматоза 1-го и 2-го типов: обзор литературыhttps://orcid.org/0000-0001-8128-2553PolatovaD. Sh.ПолатоваД. Ш.
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SavkinA. V.СавкинА. В.
Uzbekistan

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AsamedinovN. K.АсамединовН. К.
Russian Federation

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Асамединов Нуриддин Камолович

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nuriddinasamedinov@yandex.ruDavletovR. R.ДавлетовР. Р.
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NurzhabovA. I.НуржабовА. И.
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NasirovS. K.НасировС. К.
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Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology, Ministry of Health of the Republic of UzbekistanРеспубликанский специализированный научно-практический медицинский центр онкологии и радиологии Минздрава Республики УзбекистанTashkent State Dental InstituteТашкентский государственный стоматологический институтTashkent Medical AcademyТашкентская медицинская академия1310202214333411210202212102022Copyright ©; 2022, Polatova D.S., Savkin A.V., Asamedinov N.K., Davletov R.R., Nurzhabov A.I., Nasirov S.K.Copyright ©; 2022, Полатова Д.Ш., Савкин А.В., Асамединов Н.К., Давлетов Р.Р., Нуржабов А.И., Насиров С.К.2022Polatova D.S., Savkin A.V., Asamedinov N.K., Davletov R.R., Nurzhabov A.I., Nasirov S.K.Полатова Д.Ш., Савкин А.В., Асамединов Н.К., Давлетов Р.Р., Нуржабов А.И., Насиров С.К.https://creativecommons.org/licenses/by/4.0https://sarbon.abvpress.ru/jour/article/view/576

Neurofibromatosis is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of neurofibromatosis: type 1 (96 of cases), type 2 (3 % of cases), and schwannomatosis (less than 1 % of cases). The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras / MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinases ) / mTOR (mammalian target of rapamycin) signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to the proteins ezrin, radixin and moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of schwannomatosis remain unclear. Inactivating mutations in the tumor suppressor genes MARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for neurofibromatosis type 1, type 2, and schwannomatosis and reviews recent clinical trials which involve neurofibromatosis patients. The aim of the study is to present the features and pathophysiology of neurofibromatosis, as well as modern diagnostic and therapeutic strategies related to this pathology. 

Нейрофиброматоз представляет собой нейрокожный синдром, характеризующийся развитием опухолей центральной или периферической нервной систем, включая головной и спинной мозг, органы, кожу и кости. Существует 3 типа нейрофиброматоза: 1-го (96 % случаев), 2-го (3 % случаев) типов и шванноматоз (менее 1 % случаев). Ген NF1 расположен на хромосоме 17q11.2, которая кодирует белок-супрессор опухоли нейрофибромин, действующий как негативный регулятор сигнальных путей Ras / MAPK (митоген-активируемая протеинкиназа) и PI3K (фосфоинозитид-3-киназа) / mTOR (мишень рапамицина млекопитающих). Ген NF2 идентифицирован на хромосоме 22q12, кодирует мерлин – белок-супрессор опухоли, родственный белкам эзрину, радиксину и моэзину, который модулирует активность сигнальных путей PI3K/AKT, Raf/MEK/ERK и mTOR. Молекулярные представления о различных формах шванноматоза остаются неясными. Инактивирующие мутации в генах-супрессорах опухолей MARCB1 и LZTR1 считаются ответственными за его развитие в большинстве случаев. Недавно были разработаны стратегии лечения НФ, направленные на конкретные генетические или молекулярные события, связанные с онкогенезом. В этом исследовании рассматриваются молекулярные пути и связанные с ними таргетные методы лечения нейрофиброматоза 1-го, 2-го типов и шванноматоза, а также представлен обзор недавних клинических испытаний, в которых участвовали пациенты с данной патологией. 

Цель исследования – представить особенности и патофизиологию нейрофиброматоза, а также современные диагностические и терапевтические стратегии, связанные с этой патологией. 

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