Breast cancer chemoresistance: Emerging importance of cancer stem cells
Surgical Oncology, 06/15/09
Chuthapisith S et al. - Review presents the evidence for the involvement of cancer stem cells (CSCs) in carcinogenesis, tumour invasion and metastases, and resistance to various forms of therapies, including chemotherapy.
What are CSCs?- Concepts of CSCs arose from the observations of the capacity to and comparability of self-renewal between stem cells and cancer cells
- A minority of tumor cells that are able to self renew and differentiate into a new tumor cell are termed CSCs
Role of CSCs in breast cancer chemoresistance:- CSCs have a high level of ATP binding cassette (ABC) transporters that protect these cells from drug damage
- These cells remain quiescent in G-null phase
- They are later induced by different stimuli to differentiate into new mature chemoresistant tumor cells
Strategies to overcome chemoresistant breast cancer by targeting breast cancer stem cells: - Traditional approach of switching to another drug does not work
- CSCs may be eliminated by selectively targeted therapies against various self-renewal signalling pathways including the Notch, Shh, BMI-1 and Wnt signalling pathways
- Targeting ABC transporter proteins may be another approach
- Biological therapy with monoclonal antibodies targeted against specific cellular surface molecules or receptors should be considered
- Targeting at the apoptotic pathway could be an attractive and therapeutically beneficial option
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