Molecular Biomarkers of Cancer Stem/progenitor Cells Associated with Progression, Metastases, and Treatment Resistance of Aggressive Cancers

The validation of novel diagnostic, prognostic, and predictive biomarkers and therapeutic targets in tumor cells is of critical importance for optimizing the choice and efficacy of personalized therapies. Importantly, recent advances have led to the identification of gene-expression signatures in cancer cells, including cancer stem/progenitor cells, in the primary tumors, exosomes, circulating tumor cells (CTC), and disseminated cancer cells at distant metastatic sites. The gene-expression signatures may help to improve the accuracy of diagnosis and predict the therapeutic responses and overall survival of patients with cancer. Potential biomarkers in cancer cells include stem cell-like markers [CD133, aldehyde dehydrogenase (ALDH), CD44, and CD24], growth factors, and their cognate receptors [epidermal growth factor receptor (EGFR), EGFRvIII, and HER2], molecules associated with epithelial-mesenchymal transition (EMT; vimentin, N-cadherin, snail, twist, and Zeb1), regulators of altered metabolism (phosphatidylinositol-3' kinase/Akt/mTOR), and drug resistance (multidrug transporters and macrophage inhibitory cytokine-1). Moreover, different pluripotency-associated transcription factors (Oct3/4, Nanog, Sox2, and Myc) and microRNAs that are involved in the epigenetic reprogramming and acquisition of stem cell-like properties by cancer cells during cancer progression may also be exploited as molecular biomarkers to predict the risk of metastases, systemic treatment resistance, and disease relapse of patients with cancer.