Notch, Wnt and Hedgehog pathways mediate CSC self-renewal, survival and drug resistance. Notch receptors are activated by cell-bound ligands (DLL, delta-like; JAG, jagged). This interaction activates Notch intracellular domain (NICD) cleavage by γ-secretase (GST). NID translocates to the nucleus and triggers CSL/RBPJ transcription factor (TF) and Hey repressors. Wnt molecules bind to specific receptors (LPR, lipoprotein receptor and FZD, frizzled), thereby favoring β-catenin (CTNNB) stabilization by Dishevelled (DVL) complex. CTNBB translocates to the nucleus and activate CSL/RBPJ TF. Hedgehog molecules bind to patched receptor (PTCH) and inhibit Smoothened (SMOH), which allows GLI TF stabilization and further translocation into the nucleus. Modified from [18] with permission from Bentham Science Publishers LTD.