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Study of Anticancer Effect of New Low-molecular-weight PIKK Inhibitors
Kulhavá, Monika ; Řezáčová, Martina (advisor) ; Pejchal, Jaroslav (referee) ; Vinklárek, Jaromír (referee)
Conventional radiotherapy and chemotherapy interfere with the basic functions of dividing cells and are very effective againts rapidly proliferating tumor cells. They are still an indispensable tool in the fight against cancer, but their interventions also affect healthy cells and cause a number of side effects. Due to the instability of the gemone of tumor cells and frequent mutations, increased aggressiveness and resistence to treatment can occur. Tumor resistence to treatment is a very serious problem. There are a number of mechanisms by which cells defend themselves. One of the fundamental causes of resistence is the natural ability of all cells to repair damaged DNA. On the one hand, this is indispensable for cell life. On the other hand, it reduces the effect of chemotherapy or radiotherapy, which are based on the principle of causing DNA lesions. Small interventions in the signaling pathways of the cell's repair system can contribute to increasing the effectiveness of cytotoxic treatment. DNA-PK is serine/threonine kinase that is activated by DNA double-strand breaks which are considered the most lethal type of damage caused by radiation and some chemotherapy drugs. Activation of this kinase triggers signaling cascades that can lead to DNA repair, cell cycle arrest, or apoptosis. By...
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