Genetika rektalnog karcinoma i nove terapijske mogućnosti

master's thesis

• Title (english): Genetics of rectal cancer and novel therapies
• Author: Hana Garaj
• Mentor: Jasmina Marić Brozić (mentor)
• Committee member: Nikola Đaković (predsjednik povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Committee member: Jasmina Marić Brozić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Clinical Oncology); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract

Kolorektalni karcinom (KRK) je treći malignitet po incidenciji, a drugi prema mortalitetu u svijetu. Uzrokuje 1 od 10 slučajeva i smrti od raka. Kolorektalni je karcinom velik socijalni, javnozdravstveni i ekonomski problem. Etiologija je multifaktorijalna, nastaje kombinacijom genetičkih i okolišnih čimbenika. Genetički čimbenici, među njima i nasljedni sindromi poput familijarne adenomatozne polipoze i Lynchova sindroma, utječu na razvoj otprilike trećine KRK-a. Okolišne čimbenike koji utječu na razvoj KRK-a dijelimo na čimbenike prehrane i čimbenike životnog stila. KRK je genetski heterogena bolest. Nastaje uglavnom postupnim stjecanjem genetskih i epigenetskih promjena koje potiču inicijaciju, promociju i progresiju normalnih epitelnih stanica u adenome, zatim karcinome te metastaze. Genomska je nestabilnost bitna karakteristika koja prati nakupljanje tih mutacija. U KRK-u opisana su najmanje 3 različita molekularna puta genomske nestabilnosti uključujući kromosomsku nestabilnost (CIN), mikrosatelitsku nestabilnost (MSI) i fenotip CpG otoka metilatora (CIMP). Kako je rektalni karcinom još uvijek bolest koju je teško liječiti, iako postoje mnoge dostupne terapijske mogućnosti među kojima su totalna neoadjuvantna terapija, „watch and wait“ strategija, neki oblici imunoterapije i neki drugi novi oblici sustavne terapije, ishodi su često suboptimalni. Zato se i nadalje traga za novim terapijskim mogućnostima.

Abstract (english)

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death in the world. It causes 1 in 10 cancer cases and deaths. Colorectal cancer is a major social, public health and economic problem. The etiology is multifactorial, resulting from a combination of genetic and environmental factors. Genetic factors, among them hereditary syndromes such as familial adenomatous syndrome and Lynch syndrome, influence the development of about a third of CRC. Environmental factors that influence the development of CRC are divided into dietary factors and lifestyle factors. CRC is a genetically heterogeneous disease. It occurs mainly through the gradual acquisition of genetic and epigenetic changes that encourage the initiation, promotion and progression of normal epithelial cells into adenomas, then carcinomas and metastases. Genomic instability is an important characteristic that accompanies the accumulation of these mutations. At least 3 different molecular pathways of genomic instability have been described in CRC including chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Since rectal cancer is still a disease difficult to treat, although there are many available therapeutic options including total neoadjuvant therapy, watch and wait strategy, some forms of immunotherapy and some other new forms of systemic therapy, outcomes are often suboptimal. Therefore, the search for new therapeutic possibilities continues.

• Keywords: kolorektalni karcinom; genomska nestabilnost; imunoterapija; neoadjuvantna terapija
• Keywords (english): colorectal cancer; genomic instability; immunotherapy; neoadjuvant therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:008681
• 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: 2024-07-02 21:05:57