Molecular-Genetic Basis of Gastrointestinal Stromal Tumor Personalized Therapy by Receptor Tyrosine Kinase Inhibitors (A Review)

2021 ◽  
Author(s):  
M. T. Kozinova ◽  
G. A. Abalakov ◽  
D. V. Sharipova ◽  
N. L. Shimanovsky
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Genetic Basis ◽  
Kinase Inhibitors ◽  
Molecular Genetic ◽  
Personalized Therapy ◽  
Molecular Genetic Basis ◽  
Receptor Tyrosine Kinase Inhibitors

scholarly journals The mechanisms of sensitization of gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitors

2019 ◽  
Vol 100 (2) ◽  
pp. 245-251
Author(s):  
P D Dunaev ◽  
A R Galembikova ◽  
S V Boichuk
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tumor Cells ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Topoisomerase Ii ◽  
Kinase Inhibitors ◽  
Stromal Tumor ◽  
Topoisomerase Ii Inhibitors ◽  
Receptor Tyrosine Kinase Inhibitors

Aim. To examine the ability of receptor tyrosine kinase inhibitors to modulate gastrointestinal stromal tumor cells sensitivity to DNA topoisomerase II inhibitors. Methods. The following receptor tyrosine kinase inhibitors were used in the present study - imatinib, crizotinib, cabozantinib and sunitinib. An ability of the named medications to sensitize gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitor (doxorubicin) was examined by using an MTS-based colorimetric assay. The expression of apoptotic, DNA damage and repair markers was assessed with western blotting by using the corresponding monoclonal antibodies. Proliferative activity was examined in a real-time by utilizing an iCELLigence system (ACEA Biosciences Inc., USA). Results. We found that all above-mentioned receptor tyrosine kinase inhibitors were able to sensitize gastrointestinal stromal tumor cells to topoisomerase II inhibitors. This leads to the decrease of proliferative activity of tumors cells and enhancement of apoptotic cell death. Importantly, this effect was observed in imatinib-resistant gastrointestinal stromal tumor cells. One of the possible molecular mechanisms responsible for sensitization of these cells to topoisomerase II inhibitors was the ability of the target medications to inhibit the homologous recombination. This is evidenced by substantial decrease of Rad51 recombinase expression as a result of receptor tyrosine kinase inhibitor effect on the cells with DNA damage caused by topoisomerase II inhibitors. Conclusion. Receptor tyrosine kinase inhibitors are able to sensitize imatinib-resistant gastrointestinal stromal tumor cells to topoisomerase II inhibitors by inhibiting DNA homologous recombination.

Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors

2010 ◽  
Vol 20 (20) ◽  
pp. 6129-6132 ◽  
Author(s):  
Chih-Hung Chen ◽  
On Lee ◽  
Chung-Niang Yao ◽  
Meng-Yun Chuang ◽  
Yow-Lone Chang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Receptor Tyrosine Kinase Inhibitors
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