Abstract
Abstract Breast cancers contain cell populations that display hierarchical organization at the apex of which are cells that display stem cell properties. These cancer stem cells (CSCs) mediate metastasis and contribute to treatment resistance. CSC's display cellular plasticity , a property that allows them to transition between mesenchymal and epithelial states, facilitating metastasis. Although different therapeutic strategies have been developed for the treatment of the various molecular subtypes of breast cancer, CSCs driving these cancers may share common regulatory pathways including those maintaining cellular plasticity. This suggests that therapeutic strategies targeting these CSC pathways may be complementary to subtype specific therapeutic agents targeting bulk cell populations. Furthermore, since CSCs constitute a minor fraction of total tumor cell populations classical clinical endpoints such as tumor regression are inadequate to assess the efficacy of CSC targeting therapeutics. Neoadjuvant trial designs allow for the direct assessment of treatment on biological targets and as well as the therapeutic effectiveness of CSC targeting agents. Molecular analysis of circulating tumor cells at single cell resolution provides an alternative method of accessing the effects of CSC targeting therapies. CSCs are regulated by the tumor micro environment and recent studies suggest that the immune microenvironment plays a crucial role in CSC regulation. Immunotherapeutic approaches may provide a means to target heterogeneous CSC's as well as bulk tumor populations. Early phase clinical trials currently in progress have demonstrated the safety of CSC targeting agents. Future randomized trials will be required to determine whether addition of CSC targeting therapeutics to current agents targeting bulk cell populations improves the efficacy of these therapeutic agents. Citation Format: Wicha MS. Targeting breast cancer stem cells: Challenges and opportunities [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr DL-1.
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