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0225U005025,
(0124U003418)
,
Combo treatment with radiation and targeted therapy to defeat tumor radioresistance
Кореляція ідентифікованих сигнальних шляхів і генних сигнатур з клінічними результатами та патологічними параметрами пацієнтів із GBM і PCa та оцінка дії хімічних інгібіторів
Telegeev Gennadii D., Доктор біологічних наук
24-12-2025
Institute of Molecular Biology and Genetics of NAS of Ukraine
this project aims to identify gene signatures and mechanisms associated with high tumor radioresistance to PT and PBT and worse clinical outcomes of the patients with PCa and GBM treated with radiotherapy and to develop novel approaches for tumor radiosensitization. The results of this project, in the long perspective, might help develop novel clinically relevant biomarkers and radiosensitizers for different types of solid tumors.
The relative expression of Syncytin 1, Syncytin 2, Syncytin 1 (non-spliced), Syncytin 2 (non-spliced), ALDH1A3, MMP2, MMP9 genes in PC3 Mix cells as a result of photon irradiation was assessed.A decrease in the expression of ALDH1A3, Syncytin1 and Syncytin 2 in response to cultivation with the glioblastoma chemotherapy agent temozolomide was shown. Photon radiotherapy was shown to affect the expression of the studied genes CTPS1, TRIO, DDB2 in DU145 cells, although this effect is insignificant and does not exceed 25%.Photon radiotherapy reveals a decrease in TRIO gene expression at 2 Gy, an increase in DDB2 expression at 6 Gy, and an increase in CTPS1 expression at 4 Gy and 6 Gy.Proton radiotherapy alters the expression of CTPS1, TRIO, and DDB2 genes.The increase in CTPS1 expression was proportionally correlated with the increase in radiation level and may be promising for further in-depth study.RNA sequencing of DU145 prostate cancer cells after proton and photon irradiation revealed a cohort of differentially expressed genes involved in the unfolded protein response (UPR) affecting p53, EGF/PDGF signaling, heat shock proteins, and chaperones.One of the identified genes, NUPR1, was functionally analyzed using radiobiological methods and sphere formation assays.It was shown that the reduction of NUPR1 expression in DU145 and LNCaP prostate cancer cells increases their radiosensitivity.The effect of a number of chemical inhibitors on the detected molecular pathways was evaluated.The correlation of the identified signaling pathways and gene signatures with clinical outcomes and pathological parameters obtained from patients with GBM and PCa has been evaluated.
Mykhaylo V. Dybkov
Olha V. Anopriienko
Svitlana V. Antonenko
Olena S. Romantsova
2025-12-24
Updated: 2025-12-24
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