Therapeutic Potential for Targeting Autophagy in ER plus Breast Cancer

Simple Summary While ER+ breast cancer is generally considered to have a better prognosis than other breast cancer subtypes, relapse may nevertheless occur years after diagnosis and treatment. Despite initially responding to treatment, 30-40% of tumors acquire resistance to treatment that contributes to disease recurrence, metastasis, and ultimately, death. In the case of the individual estrogen antagonists or aromatase inhibitors, the autophagy induced by these agents is largely cytoprotective. However, whether autophagy inhibition will prove to be a useful strategy for improving outcomes for current combination therapeutic strategies awaits further studies. While endocrine therapy remains the mainstay of treatment for ER-positive, HER2-negative breast cancer, tumor progression and disease recurrence limit the utility of current standards of care. While existing therapies may allow for a prolonged progression-free survival, however, the growth-arrested (essentially dormant) state of residual tumor cells is not permanent and is frequently a precursor to disease relapse. Tumor cells that escape dormancy and regain proliferative capacity also tend to acquire resistance to further therapies. The cellular process of autophagy has been implicated in the adaptation, survival, and reactivation of dormant cells. Autophagy is a cellular stress mechanism induced to maintain cellular homeostasis. Tumor cells often undergo therapy-induced autophagy which, in most contexts, is cytoprotective in function; however, depending on how the autophagy is regulated, it can also be non-protective, cytostatic, or cytotoxic. In this review, we explore the literature on the relationship(s) between endocrine therapies and autophagy. Moreover, we address the different functional roles of autophagy in response to these treatments, exploring the possibility of targeting autophagy as an adjuvant therapeutic modality together with endocrine therapies.

Automated summary

This article reviews the relationship between endocrine therapies and autophagy, exploring the different functional roles of autophagy in response to these treatments. It is found that autophagy can have cytoprotective, non-protective, cytostatic, or cytotoxic effects on tumor cells, suggesting its potential as an adjuvant therapeutic modality for endocrine therapies.