Veza između inhibicije translezijske sinteze i uspješnije kemoterapije

undergraduate thesis

• Title (english): Inhibition of translesion synthesis in chemotherapy
• Author: Marija Šimić
• Mentor: Ivana Ivančić Baće (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-07-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Translezijska sinteza važna je u smanjivanju citotoksičnosti egzogenih i endogenih čimbenika koji mogu oštetiti DNA. Može smanjiti nestabilnost genoma i replikacijski stres uslijed oštećenja DNA i time suprimirati nastanak raka. S druge strane, smanjivanjem onkogen-induciranog replikacijskog stresa može potaknuti razvoj raka. Dakle, utjecaj translezijske sinteze na pojavu i razvoj raka može biti dvojak i ovisi o staničnom kontekstu. Također, obzirom na smanjenu točnost polimeraza translezijske sinteze, mutacije koje pritom mogu nastati doprinose nastanku stečene kemorezistencije. Stečena kemorezistencija često je prisutna kod tumora koji su se vratili nakon preboljenja i povećava stopu smrtnosti zbog otežanog liječenja. Translezijska sinteza ključna je i u intrinzičnoj kemorezistenciji tolerirajući oštećenja DNA u tumorskim stanicama tretiranim kemoterapeuticima. Iz više navedenih razloga inhibitori translezijske sinteze obećavajuće su rješenje u povećanju učinkovitosti kemoterapije. Brojni inhibitori pokazali su izvrsne rezultate u istraživanjima na tumorskim stanicama in vitro, no još uvijek nedostaju temeljita istraživanja in vivo i klinička istraživanja prije nego li se ovakvi inhibitori krenu koristiti u liječenju raka.

Abstract (english)

Translesion synthesis is important in reducing cytotoxicity of the external and internal factors that can damage DNA. It can reduce genome instability and replication stress caused by DNA damage, suppressing cancer development that way. On the other hand, reducing oncogen-induced replication stress can stimulate cancer development. Therefore, translesion synthesis can affect cancer development in both ways, depending on the cellular context. Moreover, translesion synthesis DNA polymerases replicate in a low fidelity manner causing mutations. Mutagenic role of TLS polymerases is central to acquired chemoresistance. Acquired chemoresistance is very likely to be present in the relapsed tumors which is why the treatments get less effective and overall survival rate is much lower for those patients. Bypassing DNA lesions in tumor cells is significant to the intrinsic drug resistance. That being said, TLS inhibitors could be promising solution to the chemoresistance problem in chemotherapy. Many inhibitors have already shown excellent results in experiments in vitro, but there are still many in vivo experiments and clinical trials required before TLS inhibitors become implemented in the cancer treatments.

• Keywords: DNA lezije; Kemorezistencija; Liječenje raka; Mutacije; Replikacija DNA
• Keywords (english): Cancer treatment; Chemoresistancy; DNA lesions; DNA replication; Mutations
• Language: croatian
• URN:NBN: urn:nbn:hr:217:267270
• Study programme: Title: Ecology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-09-03 07:02:19