Mehanizmi otpornosti stanica tumora na kemoterapeutike

undergraduate thesis

• Title (english): Resistance mechanisms of tumor cells against chemotherapeutics
• Author: Antonio Hrvat
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2017-08-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Neoplazma ili novotvorina je tkivna promjena nastala abnormalnim procesima rasta koja može i ne mora formirati masu. Da bi došlo do formiranja neoplazmi i neoplastičnih stanica one moraju proć kroz razne transformacijske procese poput metaplazije ili displazije prouzrokovane oštećenjem DNA. Ti procesi sami za sebe ne moraju nužno voditi prema neoplaziji, njoj prethodi akumuliranje velikog broja genetskih promjena kroz dugi niz godina. Takve jednom transformirane tumorske stanice mogu se klasificirati prema svojoj diferenciranosti i staničnom odnosno tkivnom tipu iz kojega potječu. Velika pojavnost takvih oboljenja gdje prema projekcijama 39.6% ljudi tijekom života će biti dijagnoziran rak dovelo je do iznimne potrebe za razvitkom dijagnostičke, farmaceutske i biotehnološke industrije usmjerne prema borbi protiv tumorskih oboljenja. Pri liječenju tih bolesti najčešće korištena sredstva su kemoterapeutici čija primarna funkcija je uništavanje tumorskih stanica kroz razne mehanizme kao što su primjerice blokiranje replikacijskih enzima, bitnih staničnih signalnih proteina, metaboličkih puteva te kroz izmjenu imunoregulacije ili induciranje apoptoze. Česta manjkavost kemoterapije očituju se u činjenici da nije uspješna u svim slučajevima, a i kada pomaže neće nužno uvijek dovesti do totalnog uništenja tumora. Glavni razlog tog problema kemoterapeutskih režima je razvitak otpornosti kod tumorskih stanica koja se postiže kroz hiperprodukciju raznih zaštitnih proteina primjerice p-glikoproteina i PD-L1, genetički zbog moduliranja ekspresije i amplifikacije određenih gena, epigenetički zbog kromatinskog i histonskog remodeliranja te interaktomski zbog utjecaja na razne unutarstanične signalne puteve. Upravo zbog takvih mehanizama veliki dio eksperimentalnih onkoloških istraživanja se odnosi na dizajniranje inovativnih tretmana za dokidanje otpornosti takvih rezistentnih stanica.

Abstract (english)

Neoplasm is an abnormal tissue change caused by aberrant growth processes which can sometimes lead to mass formation. For formation of neoplasms and neoplastic cells healthy cells need to undergo transformation such as metaplasia and dysplasia which are caused by DNA damage. These processes by themselves do not necessarily lead to neoplasia, but accumulation of many genetic mutations over long period of time will increase the likelihood. Once transformed tumor cells can be classified by degree of their differentiation and cellular or tissue type they originate from. High occurence of neoplastic disease where it is projected that 39.6% of general population will be diagnosed with cancer in a lifetime led to significant need for development of diagnostic, pharmaceutical and bioindustries aimed at solving this problem. When treating the most used agents are chemotherapeutics whose primary function is the destruction of tumor cells thought many different mechanisms, such as, inhibition of replication enzymes, blocking of cellular and metabolism pathways and immunoregulation or induction of apoptosis. Often chemotherapy is not succesful and when it is does not necessarily lead to complete destruction of tumor. Resistance is a major cause of treatment failure in chemotherapeutic drugs which is attained through overproduction of protective proteins such as p-glycoproteins and PD-L1, genetically through modulation of expression and gene amplification, epigenetically through chromatin and histone remodeling and interactomic by influencing cellular pathways. Because of these mechanisms great deal of experimental oncological research is focused on designing innovative treatments for overcoming chemotherapeutic resistance.

• Keywords: neoplazma; kemoterapeutici
• Keywords (english): neoplasm; chemotherapeutics
• Language: croatian
• URN:NBN: urn:nbn:hr:217:166844
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-09-18 12:04:02