"GENINCA will address two tumor entities, for which we have good access to pre-malignant lesions and in which genomic instability is a common feature: colorectal and liver cancer. Colorectal cancer amounts to 13.2% of all incident cases of cancer, the second most common form of cancer, surpassed only by lung cancer (13.3%). Liver cancer accounts for about 2% of total cancers, however, the most common liver cancer, i.e. hepatocellular carcinoma (HCC), is among the most lethal form of cancer, and its incidence in Europe has been steadily rising over the last few decades. GENINCA represents a collaborative study of 8 academic and 3 industrial partners from 5 European countries. GENINCA will focus on exploring pre-cancerous and cancer lesions of the two aforementioned tumor entities and their respective microenvironment. As the recent identification of human colon-cancer initiating cells by one of our academic consortium members paves the way for completely new strategies for studying mechanisms of tumorigenesis, a particular focus of this grant proposal will be the detailed characterization of these cancer initiating stem cells. At present, it is still a matter of debate which genomic changes are already present in precursor lesions and whether these lesions already show genetic instability. We will therefore address the occurrence of genomic instability and explore their underlying mechanisms especially in pre-cancerous and early cancer lesions. This will be greatly facilitated by in vivo endomicroscopy approaches, sophisticated animal models and large-scale genomic and proteomic analyses. Furthermore, we will include an in-depth analysis of the corresponding microenvironment. As this represents a translational research effort, we expect to identify markers for novel therapeutic and/or preventative strategies, as well as to facilitate tumor diagnosis, prognosis, and monitoring."