Ciljano liječenje karcinoma pluća

master's thesis

• Title (english): Target therapy of lung cancer
• Author: Goran Glodić
• Mentor: Marko Jakopović (mentor)
• Committee member: Miroslav Samaržija (predsjednik povjerenstva)
• Committee member: Nikola Đaković (član povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2016-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Rak pluća vodeći je uzrok smrti među karcinomima, kako u Hrvatskoj tako i u svijetu. Najčešća je zloćudna novotvorina u muškaraca, a treća po učestalosti u žena u Republici Hrvatskoj. Razvoj terapije raka pluća tekao je sporo do posljednjih desetak godina. Napretkom molekularno genetičkih istraživanja došlo je do otkrića pogonskih mutacija i lijekova koji ciljano inhibiraju iste. Ove spoznaje primjenjuju se diljem svijeta u terapiji adenokarcinoma pluća kod kojeg se svi bolesnici rutinski testiraju na EGFR i ALK mutacije te liječe inhibitorima tirozin kinaza EGFR i ALK poput erlotiniba, gefitiniba i crizotiniba. Inhibitori tirozin kinaze EGFR i ALK značajno su poboljšali kvalitetu života i duljinu preživljenja bolesnika oboljelih od adenokarcinoma pluća, međutim pojavio se problem razvoja rezistencije na te lijekove te potreba za novim ciljanim lijekovima za bolesnike sa razvijenom rezistencijom. Kod ostalih histoloških tipova još nisu otkrivene pogonske mutacije koje bi bile pogodne za razvoj učinkovitih ciljanih lijekova. Postoje pretkliničke i kliničke studije koje ukazuju na moguće molekularne ciljeve kod sitnostaničnog i karcinoma pluća pločastih stanica. Kroz ovaj pregledni rad prikazat će se trenutačno stanje primjene ciljane terapije u liječenju bolesnika oboljelih od karcinoma pluća, razvoj ciljanih lijekova za liječenje karcinoma pluća, studije kojima je dokazana njihova učinkovitost te mogući ciljevi za ciljanu terapiju budućnosti.

Abstract (english)

Lung cancer is the leading cause of cancer related death in the world. It is the most common malignant disease in the Republic of Croatia among men and third most common among women. Lung cancer therapy evolved slowly until the last decade, when advances in molecular science and genetics led to the discovery of driver mutations and the development of target drugs to inhibit those mutations. Target therapy of lung adenocarcinoma became the standard of care for patients harbouring EGFR and ALK mutations. Lung adenocarcinoma patients are routinely screened for EGFR and ALK mutations and treated with tyrosine kinase inhibitors like erlotinib, gefitinib and crizotinib which increased the survival and provided better quality of life for those patients. Unfortunately, resistance to these drugs is becoming a bigger issue and the development of new target drugs to overcome it is a priority. Driver mutations in small cell lung cancer and squamous cell lung cancer are being studied intensively, but no effective target drugs have been developed yet. However, several promising potentialy druggable mutations have been discovered in preclinical and clinical studies. In this review, we will address the current status of clinically relevant driver mutations, drugs that are currently being used in lung cancer target therapy and their development through recent years, studies that have proven their effectiveness and potential driver mutations that could be the target for future drug development.

• Keywords: ciljana terapija; rak pluća; pogonske mutacije
• Keywords (english): lung cancer; target therapy; driver mutations
• Language: croatian
• URN:NBN: urn:nbn:hr:105:884880
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-06-23 09:17:19