From Micro to Long: Non-Coding RNAs in Tamoxifen Resistance of Breast Cancer Cells

SIMPLE SUMMARY: Breast cancer is a disease that affects thousands of women around the world. Adequate treatment depends on the characterization of breast cancer subtypes. Tumors that are positive for the estrogen receptor represent the most common subtypes and have the best prognosis. However, many patients relapse due to resistance to tamoxifen, one of the main drugs used for these subtypes. In this study, our goal is to discuss a class of molecules that have been directly linked to the tamoxifen resistance process but is still underexplored: the non-coding RNAs (ncRNAs). We have reviewed ncRNAs that have been associated with different processes of resistance to tamoxifen in order to stimulate a discussion about the importance of knowing and understanding the role of these molecules in breast cancer and their relevance to clinical applications. ABSTRACT: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women. Two thirds of patients are classified as hormone receptor positive, based on expression of estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and/or progesterone receptor, which is regulated by ERα. Despite presenting the best prognosis, these tumors can recur when patients acquire resistance to treatment by aromatase inhibitors or antiestrogen such as tamoxifen (Tam). The mechanisms that are involved in Tam resistance are complex and involve multiple signaling pathways. Recently, roles for microRNAs and lncRNAs in controlling ER expression and/or tamoxifen action have been described, but the underlying mechanisms are still little explored. In this review, we will discuss the current state of knowledge on the roles of microRNAs and lncRNAs in the main mechanisms of tamoxifen resistance in hormone receptor positive breast cancer. In the future, this knowledge can be used to identify patients at a greater risk of relapse due to the expression patterns of ncRNAs that impact response to Tam, in order to guide their treatment more efficiently and possibly to design therapeutic strategies to bypass mechanisms of resistance.