Targeting cancer stem cells: Modulating apoptosis and stemness

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and the second leading cause of cancer mortality in Europe. Stage of disease at initial presentation determines treatment strategy. Different types of treatment are available for patients with CRC. This thesis is an overview of the research that I performed to understand therapy resistance in CRC and to identify novel treatments to improve therapy. First, in chapter 2 we summarize the findings that cancer stem cells (CSCs) are resistant to tumor therapy and I also discuss the effort that has been taken to target these therapy resistant cells. In chapter 3 we generate a colon-CSCs signature and we use this set of genes to predict outcome in stage II CRC patients. We show that not the numbers of CSCs in tumors but the methylation of a set of WNT target genes can stratify stage II CRC patients with good or bad prognosis. In the general introduction of this thesis (chapter 1) we therefore address heterogeneity in CRC that is determined by genetic and epigenetic alterations. In chapter 4 and the following chapters we study therapy resistance in colon-CSCs