Abstract
Simple SummaryBreast 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.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.
Highlights
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women [1]
Hormone receptors include the estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and the progesterone receptor (PR), a gene regulated by ER, both acting as hormone-dependent transcription factors
After a systematic review of the literature according to our research strategy, we gathered information about 75 different miRNAs in a total of 71 studies and about 22 different Long non-coding RNAs (lncRNAs) in a total of 34 studies
Summary
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women [1]. Breast tumors can be classified in clinical practice as hormone receptor and/or HER2 positive (HR+ and/or HER2+) vs negative (HR- and/or HER2-) by immunohistochemical detection or as luminal A, luminal B, HER2-enriched and basal-like according to transcriptome profiling using gene signatures such as PAM50 [2]. Hormone receptors include the estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and the progesterone receptor (PR), a gene regulated by ER, both acting as hormone-dependent transcription factors. HR+ tumors are positive for ER and/or progesterone receptor (PR). The HR+HER2- subtype is the most common, representing around 73% of all occurrences, and generally has a good prognosis. The HR+HER2+ subtype has a higher cell proliferation index and usually a more aggressive phenotype, constituting 11% of occurrences [3]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.