Uloga gena KRAS u dijagnostici i terapiji kolorektalnog karcinoma

master's thesis

• Title (english): Role of gene KRAS in the diagnosis and treatment of colorectal cancer
• Author: Zrinka Madunić
• Mentor: Nino Sinčić (mentor)
• Committee member: Zlatko Marušić (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Nino Sinčić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Genetics, Genomics and Proteomics

Abstract

Uloga KRAS gena u dijagnostici i terapiji kolorektalnog karcinoma
Zrinka Madunić

Kolorektalni karcinom (CRC) je heterogena bolest kako na staničnoj tako i na molekularnoj razini. Mutacije gena KRAS (engl. Kirsten rat sarcoma virus) prisutne su u otprilike 40% svih slučajeva CRC-a te često rezultiraju konstitutivnom aktivacijom istoimenog proteina. Takav, promijenjeni protein djeluje kao molekularni prekidač za neprekidno poticanje signalnih putova nizvodno, što potiče proliferaciju i preživljavanje stanica, a posljedično dovodi do tumorigeneze. Pacijenti čiji CRC sadrži stanice s mutiranim genom KRAS sveukupno imaju lošiju prognozu. Postoje različite laboratorijske metode za detekciju mutacija, s naglaskom na PCR analizu u stvarnom vremenu, Therascreen KRAS kit, StripAssay i SNaPshot. Zbog prisutnosti KRAS mutacija, skupina pacijenata s CRC-om zahtijeva preciznije terapije. KRAS protein je povijesno smatran nepristupačnim za ciljanu terapiju sve do razvoja inhibitora specifičnih za KRASG12C. Imunosupresivno okruženje KRAS mutiranog CRC-a objašnjava ograničenja imunoterapije, ali ističe i potencijalne terapijske pristupe poput adoptivnog prijenosa T limfocita usmjerenih na KRAS mutant ili cjepiva za neutralizaciju proteina KRAS. Ovi obećavajući inhibitori mogu pružiti nove strategije za liječenje KRAS-mutiranog CRC-a.

Abstract (english)

Role of KRAS gene in the diagnosis and treatment of colorectal cancer
Zrinka Madunić

Colorectal cancer (CRC) is a heterogeneous disease at the cellular and molecular level. Kirsten rat sarcoma virus (KRAS) gene is a frequently mutated oncogene in CRC, with mutations present in approximately 40% of all CRC cases. Mutations result in constitutive activation of the KRAS protein, which acts as a molecular switch to continuously stimulate downstream signalling pathways, promoting cell proliferation and survival, leading to tumorigenesis. Patients whose CRC contains cells with mutated KRAS have a worse prognosis overall. There are various laboratory methods for mutation detection, emphasizing real-time PCR analysis, Therascreen KRAS kit, and other methods such as StripAssay and SNaPshot. Due to the presence of KRAS mutations, this group of CRC patients requires more precise therapies. The KRAS protein was historically considered inaccessible to targeted therapy until the development of KRASG12C-specific inhibitors. The immunosuppressive environment of KRAS mutated CRC explains the limitations of immunotherapy, but also highlights potential therapeutic approaches such as adoptive transfer of T lymphocytes targeting the KRAS mutant or vaccines to neutralize the KRAS protein. These promising inhibitors may provide new strategies for the treatment of KRAS-mutated CRC.

• Keywords: kolorektalni karcinom; KRAS; mutacije KRAS; KRAS dijagnostika; KRAS terapija
• Keywords (english): colorectal cancer; KRAS; KRAS mutations; KRAS diagnostics; KRAS therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:492025
• 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: 2024-06-21 15:02:45