Tumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies

Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating
cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as
well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation
and identification remain largely disputed and incompletely established. In this review, we discuss the latest
developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC). We feature
recent findings on TIC-relevant signaling pathways and the metabolic identity of TICs, as well as their current
clinical implications. Lastly, we highlight the influence of inter- and intra-tumoral heterogeneity on TIC
function and targeting approaches.