Cancer Stem Cells and the Tumor Immune-Microenvironment
The Aberger lab studies signaling pathways that determine the malignant traits of rare cancer stem cells (CSC). CSC are responsible for tumor growth, metastasis and disease relapse, making them prime targets for efficient and durable therapies. In this context, the main focus of the lab is on the role of Hedgehog/GLI signaling in CSC, the tumor-microenvironment and the anti-tumoral immune response. Eradicating malignant CSC by targeted pathway inhibition and reactivation of the immune reaction against CSC is a major aim of the group.
In addition, the Aberger lab has a strong interest in understanding mechanisms of drug resistance to develop innovative and rationale-based combination treatments targeting CSC with improved efficacy und durable responses.
The lab applies a wide spectrum of state-of-the-art technologies ranging from –omics approaches to predictive in vivo cancer models and assays involving primary patient material.
This comprehensive approach has already proven successful. For instance, the Aberger lab has identified several synergistic interactions of the Hedgehog pathway, accounting for malignant progression of various cancer entities. These discoveries have laid the basis for the development of rationale-based combination treatments with improved efficacy by simultaneously targeting cooperating oncogenic signals.
Gruber W, Hutzinger M, Elmer DP, Parigger T, Sternberg C, Cegielkowski L, Zaja M, Leban J, Michel S, Hamm S, Vitt D, Aberger F. DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance. Oncotarget 2016; 7(6):7134-48.
Kern D, Regl G, Hofbauer SW, Altenhofer P, Achatz G, Dlugosz A, Schnidar H, Greil R, Hartmann TN, Aberger F: Hedgehog/GLI and PI3K signaling in the initiation and maintenance of chronic lymphocytic leukemia. Oncogene 2015 34(42):5341-51.
Pencik J, Schlederer M, Gruber W, Unger C, Walker SM, Chalaris A, Marié IJ, Hassler MR, Javaheri T, Aksoy O, Blayney JK, Prutsch N, Skucha A, Herac M, Krämer OH, Mazal P, Grebien F, Egger G, Poli V, Mikulits W, Eferl R, Esterbauer H, Kennedy R, Fend F, Scharpf M, Braun M, Perner S, Levy DE, Malcolm T, Turner SD, Haitel A, Susani M, Moazzami A, Rose-John S, Aberger F, Merkel O, Moriggl R, Culig Z, Dolznig H, Kenner L. STAT3 regulated ARF expression suppresses prostate cancer metastasis. Nat Commun. 2015 Jul 22;6:7736.
Eberl M, Klingler S, Mangelberger D, Loipetzberger A, Damhofer H, Zoidl K, et al. Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells. EMBO Mol Med 2012;4:218-33.
Teperino R, Amann S, Bayer M, Mcgee SL, Loipetzberger A, Connor T, et al. Hedgehog Partial Agonism Drives Warburg-like Metabolism in Muscle and Brown Fat. Cell 2012;151:414-26. IF: 33.1
Schnidar H, Eberl M, Klingler S, Mangelberger D, Kasper M, Hauser-Kronberger C, et al. Epidermal Growth Factor Receptor Signaling Synergizes with Hedgehog/GLI in Oncogenic Transformation via Activation of the MEK/ERK/JUN Pathway. Cancer Research 2009;69:1284-92.
Fritz Aberger, PhD
Professor of Molecular Cancer and Stem Cell Research
Deputy Head of CCS
Department of Biosciences
University of Salzburg
Cancer stem cells and the tumor microenvironment
Vivid signal cross-talk between cancer cells, rare tumor initiating cancer stem cells (CSC) and the microenvironment and the immune system drives cancer initiation, growth and metastasis. Understanding the molecular basis of these molecular communication processes will open up new opportunities for innovative therapies based on rational multimodal combination treatments