Breast cancers contain cells that act and behave in a similar manner to stem cells, and these cancer stem cells (CSCs) bring about metastasis and contribute to treatment resistance. 

Researchers at the University of Michigan Comprehensive Cancer Center provided an overview of CSCs on Thursday, December 8, during the San Antonio Breast Cancer Symposium, noting that breast cancer CSCs may have common regulatory pathways and are regulated by the tumor microenvironment. 

CSCs tend to display a property known as cellular plasticity, which allows them to transition between two types of stem cells—mesenchymal and epithelial—and enables metastasis. Therapeutic strategies targeting these CSC pathways may be complementary to subtype-specific therapeutic agents targeting bulk cell populations, the group explained.

Classical clinical endpoints such as tumor regression are typically inadequate to assess the efficacy of CSC-targeting therapeutics because CSCs are such a small fraction of the tumor cell populations. 

Neoadjuvant trial designs provide a means to directly assess the therapeutic effectiveness of CSC-targeting agents. Similarly, the molecular analysis of circulating tumor cells at single cell resolution can also assess the effects of CSC-targeting agents. Based on outcomes of recent studies, immunotherapeutic approaches may be another avenue that can target heterogeneous CSCs as well as bulk tumor populations. Ongoing, early-phase studies have demonstrated the safety of CSC-targeting agents, which may provide the incentive to move forward into later-stage trials.

The researchers said that 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.”