Petletno preživetje bolnikov s pljučnim rakom je slabo, samo 12-odstotno, in se v zadnjih 15 letih ni bistveno izboljšalo. Standardno zdravljenje razsejanega nedrobnoceličnega raka pljuč (NDRP), ki je danes najpogostejši tip raka pljuč, je kemoterapija na osnovi citostatika cisplatina. S tem je citostatsko zdravljenje razsejanega NDRP najbrž doseglo največ, kar je lahko. V zadnjih letih pa smo tudi pri zdravljenju NDRP priča razmahu tarčnega zdravljenja. Kot učinkovita so se izkazala tarčna zdravila, ki delujejo na receptor za epidermalni rastni dejavnik (EGFR), in to predvsem mali molekuli, zaviralca tirozinske kinaze (TKI) erlotinib in gefitinib. EGFR je transmembranski glikoprotein, ki se nahaja tako na površini zdravih kot tudi tumorskih celic različnih rakov. Pripada družini proteinov ErbB, ki vključuje 4 receptorje. Od vseh določanj izraženosti EGFR se je določitev aktivirajočih mutacij gena za EGFR v primarnem tumorju izkazala za najboljši pozitivni napovedni dejavnik odgovora na zdravljenje s proti EGFR usmerjenimi TKI. Čeprav je bila povezava med mutacijami gena za EGFR ter nekaterimi kliničnimi in patološkimi značilnostmi NDRP dokazana, pa na podlagi kliničnih in patoloških značilnosti bolnikov ne moremo zanesljivo prepoznati tistih, ki bodo imeli največjo korist od zdravljenja s TKI. Samo z določitvijo aktivirajočih mutacij gena za EGFR je mogoče prepoznati bolnike, ki bodo značilno bolje odgovorili na zdravljenje s TKI kot na kemoterapijo in pri katerih je ob zdravljenju s proti EGFR usmerjenimi TKI utemeljeno pričakovati razmeroma dolgo preživetje in dobro kakovost življenja. Zato je danes pri vseh bolnikih s pljučnim adenokarcinomom pred uvedbo prvega sistemskega zdravljenja napredovale bolezni priporočeno določanje mutacij gena za EGFR v primarnem tumorju. Na podlagi tega podatka je namreč mogoča ustreznejša izbira prvega in tudi poznejših redov sistemskega zdravljenja pri vsakem bolniku.The 5-year relative survival rates of patients with lung cancer are approximately 12%, and have increased only by 2.2% during the last 15 years. Third generation chemotherapy based on platinum derivates is currently a standard treatment for the advanced non-small-cell lung cancer (NSCLC) but has probably reached a plateau. With the advent of targeted therapy it has been introduced into the clinical management of advanced NSCLC as well. Epidermal growth factor (EGFR) is a transmembrane glycoprotein which is expressed on the cell surface of a tumor as well as on normal cells. It belongs to the ErbB receptor family, which includes four types of receptors. In the article only EGFR (HER1/ErbB1) will be considered. Treatment with two small molecules, tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR), namely gefintib and erlotinib, already proved to be an effective treatment strategy in patients with advanced NSCLC. Among different methods used for EGFR status determination, only identification of activating mutations in the EGFR gene domain proved to be a very reliable and significant predictor for the response to EGFRdirected TKIs therapy in NSCLC. Even though the activating EGFR mutations were found to be more frequent in patients with particular clinico-pathological characteristics, such as females, non-smokers, those with adenocarcinoma histology, a selection of patients based on these characteristics does not allow for a proper selection of patients for EGFR-directed TKI therapy. Only by determining the activating EGFR mutations in the primary tumor can the identification of NSCLC patients with expected high response rates to EGFR-directed TKI therapy leading to long survival and a good quality of life be achieved. Personalized medicine for NSCLC patients is now reality, and EGFR mutation status should be determined in the primary tumor of all patients prior to any systemic therapy for advanced disease, thus allowing us a tailored first-line and subsequent lines of systemic therapy in each individual patient
