[Frontiers in Bioscience S3, 1486-1499, June 1, 2011]

Cancer stem cells: perspectives of new therapeutical approaches for breast cancer

Andrea Nicolini1, P Ferrari1, M Fini,2 V Borsari2, P Fallahi1, A Antonelli1, Angelo Carpi3, P Miccoli4

1Department of Internal Medicine, University of Pisa, Italy, 2Laboratory of Experimental Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy, 3Department of Reproduction and Ageing, 4Department of Surgery, University of Pisa, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Identification and tumourigenicity of breast cancer stem cells (BrCSCs)
4. Breast cancer stem cells as therapeutic targets
4.1. Non immunological interventions
4.1.1. The inhibition of ABC drug transporters
4.1.2. The self-renewal signalling pathways
4.1.2.1. Hh, Notch, Wnt, Akt and mTOR signalling inhibitors
4.1.3. Epithelial to mesenchymal transition (EMT) program inhibition
4.1.4. Selective inhibition of heat shock protein 90 (HSP90)
4.1.5. Cell differentiation therapy
4.1.6. BrCSCs elimination through other interventions
4.1.6.1. Metformin
4.1.6.2. Pro-apoptotic to anti-apoptotic proteins increased ratio
4.1.6.3. EGFR, HER2/neu (erbB2) and mTOR inhibitors
4.1.6.4. Reversal of epigenetics
4.2. Immunological interventions
4.2.1. Immunotherapy targeting breast cancer stem cells
4.2.1.1. Specific antigens expressed on the cancer stem cells: ALDH1, MUC-1, ESA, CK5, CD49F
4.2.1.2. HER2 receptor
4.2.1.3. DC-based vaccination
4.2.1.4. Blockers of the extrinsic signals at CSC niche
5. Perspectives
6. References

1. ABSTRACT

Currently stem cells are hypothesized to play a central role in the origin, spread and resistance to treatment of breast cancer. Common anticancer therapy is effective but transient, with tumor relapse and metastatic disease often occurring. For therapy to be more effective, debulking of differentiated tumors must occur followed by targeting of the remaining surviving often quiescent tumor stem cells. New therapeutics aimed at cancer stem cells are achieved through non immunological and immunological methods. The former include elective ABC drug transporters or the heat shock protein 90 inhibition, targeting the self-renewal signalling pathways or the EMT program, differentiation therapy, or other interventions to eliminate BrCSCs. The latter include targeting specific antigens expressed on BrCSCs, dendritic cells (DCs) based vaccination and blockers of the extrinsic signals at CSC niche. Here all