Medizinische Universität Graz - Research portal
Selected Publication:
Pichler, A.
Identification of potential therapeutic drug combination concepts for the treatment of colorectal cancer by genome wide crispr screening.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2019.
FullText
- Authors Med Uni Graz:
- Advisor:
- Prokesch Andreas
- Altmetrics:
- Abstract:
- In colorectal cancer the MAPK pathway and its mutation BRAFV600E are implicated with tumorigenesis. Even though several drugs exist targeting the individual members of this pathway, they remain ineffective in metastatic colorectal cancer (mCRC) leaving patients with a poor survival prognosis (1). This ineffectiveness of pathway inhibitors is due to a feedback loop which engages receptor tyrosin kinases, in particular EGFR. When a downstream member of the pathway is inhibited, the feedback loop can re-activate the pathway instantaneously to maintain tumor progression (2). This study investigates the hypothesis that combination therapy can interfere with this feedback loop to enhance pathway inhibition and scrutinizes the potential therapeutic effect. By using RKO_Cas9 cells transduced with a genome wide library, drug modifier CRISPR screens were performed followed by DNA sequencing and bioinformatics analysis. Highly depleted genes, which were also involved in the MAPK signaling pathway were tested in combination in order to discover synergistic effects of combined treatment and to find potential poly-therapeutic combinations. (...)