Molecular analysis of pancreatic cancer stem cells and novel therapeutic opportunities / submitted by Andrea Loipetzberger

• VerfasserIn: Loipetzberger, Andrea
• Place / Publishing House: 2015
• Year of Publication: 2015
• Language: English
• Classification: 42.13 - Molekularbiologie; 44.81 - Onkologie
• Physical Description: 182 Bl.; Ill., graph. Darst.; 30 cm; 1 CD-ROM
• Notes: Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers

ger: Cancer involves the aberrant activation of a limited set of signaling pathways regulating processes such as proliferation, survival, motility and stemness. Cooperative interactions of oncogenic signals play a critical role in malignant transformation. Our group has previously identified synergistic interactions of two clinically relevant drug targetable pathways, the Hedgehog (HH)/GLI and the EGFR pathway (Kasper, M., H. Schnidar, et al. (2006). Mol Cell Biol 26(16):<br />6283-6298.; Schnidar, H., M. Eberl, et al. (2009). Cancer Res 69(4):<br />1284-1292.).<br />We further showed that synergistic HH/GLI-EGFR signaling regulates a defined set of "synergistic target genes" that determines the malignant phenotype of pancreatic cancer cells (Eberl M., S.Klingler, et.al (2012). EMBO Mol Med.). During my PhD thesis, I analyzed the dependency of a tumor initiating subpopulation of pancreatic cancer on the HH/GLI-EGFR signal cooperation. Chemical or shRNA mediated perturbation of either pathway, as well as perturbation of synergistic target genes abolished the tumor initiating subpopulation in vitro and reduced in vivo tumor development of pancreatic cancer cells. Building on this data we could show a hierarchical signaling network of the synergistic HH/GLI-EGFR target genes in the process of tumor development.<br />Accordingly we tested different combined treatment approaches in vitro and in vivo to identify rationale targets for a more effective therapy.<br />In addition we used an unbiased proteomics/transcriptomics approach to identify 3 new putative treatment targets for pancreatic cancer.<br />