Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC99910.15690/vramn999ONCOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ОНКОЛОГИИPROMISING TARGETED THERAPIES GENES AND PROGNOSTIC BIOMARKERS OF GASTRIC CANCERПЕРСПЕКТИВНЫЕ ГЕНЫ-МИШЕНИ ТАРГЕТНОЙ ТЕРАПИИ И ПРОГНОСТИЧЕСКИЕ БИОМАРКЕРЫ РАКА ЖЕЛУДКАhttps://orcid.org/0000-0003-4778-9726KipkeevaFatima M.КипкееваФатима Магомедовна
Russian Federation

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SPIN-код: 5902-4070

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SPIN-код: 5902-4070

BRCA1@mail.ruhttps://orcid.org/0000-0002-2345-2056MuzaffarovaTatiana A.МузаффароваТатьяна Александровна
Russian Federation

MD, PhD.

1, Moskvorechie street, 115522 Moscow.

SPIN-код: 4657-2770

Кандидат медицинских наук.

115522, Москва, ул. Москворечье, д. 1, тел.: +7 (499) 324-12-39.

SPIN-код: 4657-2770tatiana.muzaffarova@mail.ruhttps://orcid.org/0000-0002-9608-4696NikulinMaxim P.НикулинМаксим Петрович

MD, PhD.

Moscow.

SPIN-код: 9455-5566

Кандидат медицинских наук.

Москва.

SPIN-код: 9455-5566maximpetrovich@mail.ruhttps://orcid.org/0000-0001-6576-5512ApanovichPavel V.АпановичПавел Васильевич

1, Moskvorechie street, 115522 Moscow.

SPIN-код: 6748-9211

115522, Москва, ул. Москворечье, д. 1, тел.: +7 (499) 324-12-39.

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Apanovich2004@mail.ruhttps://orcid.org/0000-0002-7001-9116KarpukhinAlexander V.КарпухинАлександр Васильевич

PhD.

1, Moskvorechie street, 115522 Moscow.

SPIN-код: 2929-1276

Кандидат медицинских наук, профессор.

115522, Москва, ул. Москворечье, д. 1,тел.: +7 (499) 324-12-39.

SPIN-код: 2929-1276

karpukhin@med-gen.ruResearch Centre for Medical GeneticsФГБНУ «Медико-генетический научный центр»NN Blokhin Russian Cancer Research CentreФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»060920187342622720606201814082018Copyright ©; 2018, "Paediatrician" Publishers LLCCopyright ©; 2018, Издательство "Педиатръ"2018"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/999

Understanding the molecular genetic features of gastric cancer (GC) and principally the functioning of signaling cascades involved in its occurrence and development is determining for identifying the most promising genes for targeted therapy. On this basis, development and consequent implementation of effective drugs and treatment regimens is conducted. The inductors of signaling paths, the main one of which is the mTOR pathway, and the functioning of the pathway are considered in details. mTOR inductors (angiogenesis factors, epidermal growth factor and their receptors) are most actively studied as therapeutic targets. Particular attention is paid to the consideration of stimulation and development of lymphangiogenesis where not all genes are discovered and examined yet. The possibility of achieving a significant therapeutic effect with simultaneous inhibition of the action of genes of angio- and lymphangiogenesis is considered. The review covers the administered target drugs and pharmaceuticals under investigation for GC therapy, including immunotherapy. The review provides details on the simultaneous activation of several genes ― potential targets of therapy and possible interactions in the development of the tumor process. As a result the combined effect of the simultaneous action of two or more factors can be detected. The possibility of maintaining the activated signaling cascade when one of the activated receptors is blocked in consequence of the action of another expressed receptor is also considered. The article presents information on development of drugs affecting several targets and on effectiveness of combined therapy with different targeted drugs. Essential effectiveness of GC therapy can be achieved by personified treatment including application of molecular classification. The review discusses the prognostic value of target and other genes expression, as well as GC subtypes according molecular classification.

Представление о молекулярно-генетических особенностях рака желудка (РЖ), и в первую очередь функционировании сигнальных каскадов, задействованных в его возникновении и развитии, имеет определяющее значение для выявления наиболее перспективных генов-мишеней таргетной терапии. На этой основе проводится разработка, а затем и внедрение в практику эффективных препаратов и схем лечения. В статье подробно рассматриваются индукторы сигнальных путей и их функционирование. mTOR является основным сигнальным каскадом при многих типах рака, в том числе при РЖ. Индукторы mTOR ― факторы ангиогенеза, эпидермальный фактор роста и их рецепторы ― наиболее активно исследуются в качестве терапевтических мишеней. Особое внимание придается стимулированию и развитию лимфангиогенеза, при этом участвующие в нем гены не все пока еще вскрыты и исследованы. Приводится информация о возможном достижении существенного терапевтического эффекта при одновременном ингибировании действия генов ангио- и лимфангиогенеза. Сообщается о таргетных препаратах для терапии РЖ, как уже используемых в протоколах лечения, включая иммунотерапию, так и проходящих стадию клинических испытаний. Рассматриваются одновременная активация нескольких генов и их возможное взаимодействие при развитии опухолевого процесса, что предполагает комбинированный эффект совместного влияния двух и более факторов. Учтена также возможность сохранения активированного сигнального каскада при блокировании одного из активированных рецепторов в результате действия экспрессируемого рецептора. Сообщается о разработке препаратов, ориентированных одновременно на несколько мишеней, а также об эффективности комбинированного применения разных таргетных препаратов. Существенное значение для улучшения качества терапии РЖ может иметь персонификация лечения, в том числе с использованием молекулярной классификации. Обсуждается прогностическое значение экспрессии генов-мишеней и некоторых других генов, а также подтипов РЖ по молекулярной классификации.

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