Biološka terapija kolorektalnog karcinoma

master's thesis

• Title (english): Biological therapy for colorectal cancer
• Author: Marija Bartulović
• Mentor: Karmela Barišić (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2021-06-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Kolorektalni karcinom (CRC) jest zloćudna novotvorina epitelnih stanica sluznice debeloga crijeva i rektuma koja se javlja kod osoba starije životne dobi. U malom broju slučajeva zna se pojaviti i u ranijoj životnoj dobi, gdje je često riječ o nasljednom obliku karcinoma. Mnogo rizičnih čimbenika pridonosi razvoju karcinoma. Postoje različiti oblici nasljednoga CRC-a kod kojih je poznata molekularna pozadina bolesti. Liječenje CRC-a ovisi o stupnju napretka bolesti.
Cilj ovoga diplomskog rada bio je opisati novije lijekove koji se koriste u terapiji metastatskog kolorektalnog karcinoma (mCRC) uz standardnu kemoterapiju.
Tijekom nekoliko desetljeća postignut je značajan napredak u razvoju bioloških lijekova. Biološka terapija, odnosno monoklonska protutijela, dobiveni su biotehnološkim postupcima rekombinantne DNA tehnologije. Ti lijekovi djeluju na način da blokiraju receptor ili ligand koji se veže za taj receptor i time inhibiraju daljnju signalizacijsku kaskadu unutar stanice. Cetuksimab i panitumumab koriste se u terapiji kod osoba koje nemaju mutiran KRAS gen. Lijekovi koji djeluju na VEGF signalni put zaustavljaju tumorsku angiogenezu. Enkorafenib djeluje na stanice raka koje imaju BRAFV600E mutaciju. Lijekovi koji djeluju na imunosni sustav ciljaju na imunosupresorske molekule PD-1 (pembrolizumab, nivolumab) i CTLA-4 (ipilimumab) i tako imunosni odgovor posredovan tim molekulama ostaje očuvan. Navedeni lijekovi imaju brojne nuspojava. Najčešće su kožne reakcije, osipi, mučnina te proljev. Nažalost neke nuspojave mogu imati i smrtni ishod. Potencijalne nove kombinacije lijekova u liječenju mCRC-a su u kliničkim ispitivanjima i trebat će još neko vrijeme kako bi se ustanovila njihova djelotvornost i sigurnost. Također, potrebno je dodatno praćenje već poznatih lijekova na tržistu.

Abstract (english)

Colorectal cancer (CRC) is malignant neoplasm of the epithelial cell mucosa in colon and/or rectum region. This tumor is more common with elderly people, however, in small number of cases it can present itself in the earlier stages of life, usually as a hereditary form. There are many risk factors that contribute to the development of this type of cancer. When it comes to hereditary CRC, there are several possible molecular pathways that contribute to its development. Treatment of CRC is dependent on the stage of the cancer.
The aim of this thesis was to describe newly available medications that are used to treat the metastatic colorectal carcinoma (mCRC) alongside standard chemotherapy.
In the last few decades, there was a significant improvement in development of biological therapy. Biological therapy, or otherwise known as monoclonal antibodies, is created by using recombinant DNA technology. The mechanism these drugs work is by inhibiting cell receptor or a ligand that attaches to that receptor. By doing so, they block downstream cell-signaling cascade. Cetuximab and panitumumab are used to treat cancer cells with “wild- type” KRAS gene. Drugs that target VEGF signaling pathway diminish tumor angiogenesis. Encorafenib targets tumor cells that have BRAFV600E mutation. Drugs that work as immunotherapy target immunosuppressor molecules such as PD-1 (pembrolizumab, nivolumab) or CTLA-4 (ipilimumab). This way the immunological response remains active. Drugs mentioned above have numerous side effects. The most common side effects include skin reactions, rashes, nausea, and diarrhea. Unfortunately, some of these side effects can be fatal. Potential new drug combinations in treatment of mCRC are in clinical studies and it will take some time to determine their efficacy and safety.

• Keywords: kolorektalni karcinom; monoklonska protutijela; EGFR-receptor
• Keywords (english): colorectal cancer; monoclonal antibodies; EGFR-receptor
• Language: croatian
• URN:NBN: urn:nbn:hr:163:291478
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-02 11:08:48