Targeted therapies of metastatic breast cancer: Relationships with cancer stem cells

In the last years, many targeted agents have been developed for metastatic breast cancer (MBC) treatment and are being tested in clinical trials. In spite of this, apart from epidermal growth factor receptor 2 (HER2) positive subset, no significant increase in the median overall survival (OS) has been reported. Similarly to conventional chemo- and radiotherapy, the cancer stem cell theory has been evoked to explain the frustrating results often obtained with this emerging category of drugs. This review examines the results in MBC of the approved targeted therapies or those currently under evaluation in experimental studies or in clinical trials, in the light of their relationships with breast CSCs and of the efforts to circumvent the development of resistance. In the next, there is the principal need to investigate if the effects on CSCs may be used to overcome cancer resistance and it will be opportune to consider whether molecular targeted therapies should be used alone or combined with conventional therapy, or with a different target drug specific for CSCs.