Soft Tissue Sarcoma Study: Association of Genetic Alterationsin the Apoptosis Pathways with Chemoresistance to Doxorubicin

Kirilin, E.M.; Fetisov, T.I.; Moiseeva, N.I.; Lesovaya, E.A.; Laletina, L.A.; Makhmudova, L.F.; Manikaylo, A.E.; Fomina, L.Y.; Burov, D.A.; Bokhyan, B.Y.; Zinovieva, V.Y.; Vilkova, A.S.; Mekheda, L.V.; Kozlov, N.A.; Scherbakov, A.M.; Belitsky, G.A.; Švedas, V.K.; Kirsanov, K.I.; Yakubovskaya, M.G.

Авторы: Kirilin Evgeny M., Fetisov Timur I., Moiseeva Natalia I., Lesovaya Ekaterina A., Laletina Lidia A., Makhmudova Leyla F., Manikaylo Angelika E., Fomina Liliya Y., Burov Denis A., Bokhyan Beniamin Yu, Zinovieva Victoria Y., Vilkova Alice S., Mekheda Larisa V., Kozlov Nikolay A., Scherbakov Alexander M., Belitsky Gennady A., Švedas Vytas K., Kirsanov Kirill I., Yakubovskaya Marianna G.
Журнал: Cancers
Том: 14
Номер: 7
Год издания: 2022
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
DOI: 10.3390/cancers14071796
Аннотация: Soft tissue sarcomas (STS) are heterogeneous cancers with more than 100 histological subtypes, different in molecular alterations, which make its personalized therapy very complex. Gold standard of chemotherapy for advanced STS includes combinations of Doxorubicin and Ifosfamide or Gemcitabine and Docetaxel. Chemotherapy is efficient for less than 50% of patients and it is followed by a fast development of drug resistance. Our study was directed to the search of genetic alterations in cancer cells associated with chemoresistance of undifferentiated pleomorphic and synovial sarcomas to the abovementioned genotoxic drugs. We analyzed chemoresistance of cancer cells in vitro using primary STS cultures and performed genetic analysis for the components of apoptotic signaling. In 27% of tumors, we revealed alterations in TP53, ATM, PIK3CB, PIK3R1, NTRK1, and CSF2RB. Cells from STS specimens with found genetic alterations were resistant to Dox, excluding the only one case when TP53 mutation resulted in the substitution Leu344Arg associated with partial oligomerization loss and did not cause total loss of TP53 function. Significant association between alterations in the components of apoptosis signaling and chemoresistance to Dox was found. Our data are important to elaborate further the therapeutic strategy for STS patients with alterations in apoptotic signaling.
Добавил в систему: Фетисов Тимур Игоревич

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Soft Tissue Sarcoma Study: Association of Genetic Alterationsin the Apoptosis Pathways with Chemoresistance to Doxorubicinстатья

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