Recent studies in the field of cancer stem cells have revealed that the 
alterations in key gene products involved in the epithelial-mesenchymal 
transition (EMT) program, altered metabolic pathways such as enhanced 
glycolysis, lipogenesis and/or autophagy and treatment resistance may occur in 
cancer stem/progenitor cells and their progenies during cancer progression. 
Particularly, the sustained activation of diverse developmental cascades such as 
hedgehog, epidermal growth factor receptor (EGFR), Wnt/β-catenin, Notch, 
transforming growth factor-β (TGF-β)/TGF-βR receptors and/or stromal 
cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) can play critical 
functions for high self-renewal potential, survival, invasion and metastases of 
cancer stem/progenitor cells and their progenies. It has also been observed that 
cancer cells may be reprogrammed to re-express different pluripotency-associated 
stem cell-like markers such as Myc, Oct-3/4, Nanog and Sox-2 along the EMT 
process and under stressful and hypoxic conditions. Moreover, the enhanced 
expression and/or activities of some drug resistance-associated molecules such 
as Bcl-2, Akt/molecular target of rapamycin (mTOR), nuclear factor-kappaB 
(NF-κB), hypoxia-inducible factors (HIFs), macrophage inhibitory cytokine-1 
(MIC-1) and ATP-binding cassette (ABC) multidrug transporters frequently occur 
in cancer cells during cancer progression and metastases. These molecular events 
may cooperate for the survival and acquisition of a more aggressive and 
migratory behavior by cancer stem/progenitor cells and their progenies during 
cancer transition to metastatic and recurrent disease states. Of therapeutic 
interest, these altered gene products may also be exploited as molecular 
biomarkers and therapeutic targets to develop novel multitargeted strategies for 
improving current cancer therapies and preventing disease relapse.