Breast cancer: Muscarinic receptors as new targets for tumor therapy

Abstract

The development of breast cancer is a complex process that involves theparticipation of different factors. Several authors have demonstrated the overexpressionof muscarinic acetylcholine receptors (mAChRs) in different tumortissues and their role in the modulation of tumor biology, positioning them astherapeutic targets in cancer. The conventional treatment for breast cancerinvolves surgery, radiotherapy, and/or chemotherapy. The latter presentsdisadvantages such as limited specificity, the appearance of resistance totreatment and other side effects. To prevent these side effects, several schedules ofdrug administration, like metronomic therapy, have been developed. Metronomictherapy is a type of chemotherapy in which one or more drugs are administeredat low concentrations repetitively. Recently, two chemotherapeutic agents usuallyused to treat breast cancer have been considered able to activate mAChRs. Thecombination of low concentrations of these chemotherapeutic agents withmuscarinic agonists could be a useful option to be applied in breast cancertreatment, since this combination not only reduces tumor cell survival withoutaffecting normal cells, but also decreases pathological neo-angiogenesis, theexpression of drug extrusion proteins and the cancer stem cell fraction. In thisreview, we focus on the previous evidences that have positioned mAChRs asrelevant therapeutic targets in breast cancer and analyze the effects of administeringmuscarinic agonists in combination with conventional chemotherapeuticagents in a metronomic schedule.