Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

Abstract

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China

“… claimed that miR‐21‐5p mediated cellular proliferation, invasion, migration, and apoptosis by targeting PTEN, RECK, and Bcl‐2 in LSCC. At present, a robust association of miR‐21‐5p expression in tumors with diagnostic effect was also observed in numerous solid tumors, such as colorectal cancer , gastric cancer , breast cancer , pancreatic cancer , and so on. Moreover, overexpression of miR‐21‐5p was correlated with poor survival of the patients with pancreatic cancer and gastric cancer .…”

MicroRNA and cancer: a focus on mammary tumors in female dogs

“…It has been suggested that miRNAs may be key modifiers of chemo-resistance and as promising therapeutic targets in human breast cancer (TANG et al, 2012;CAMPOS-PARRA et al, 2017). BOCKHORN et al (2013) reported that high levels of miR-30c make breast cancer cells more sensitive to paclitaxel and doxorubicin treatment in preclinical models.…”

MiR-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility

“…1 Different molecules decide different subtypes and therefore lead to different therapeutic strategies and clinical outcomes. 2 Up to now, there have only been two biomarkers used to guide therapeutic strategies despite the stage of breast cancer: estrogen receptor (ER) and the Human Epidermal growth factor Receptor 2 (HER2). 3 Although current therapies constitute a considerable improvement in breast cancer treatments, there are still some types of breast cancer existing with tumor progression and therapyresistance.…”

“…3 Although current therapies constitute a considerable improvement in breast cancer treatments, there are still some types of breast cancer existing with tumor progression and therapyresistance. 2,3 Therefore, to gure out the molecular mechanisms of breast cancer is an urgent requirement for the treatment of breast cancer.…”

“…5 Since miRNAs dysregulated in breast cancer in 2005, more and more studies about miRNAs in breast cancer have been reported, including onco-miRNAs (suppressing tumor suppressor genes) and tumor-suppressor miRNAs (downregulating oncogenic genes). 2,6 LIM domain kinase 1 (LIMK1) is a serine/threonine kinase that regulates actin polymerization through phosphorylation and inactivation colin (CFL1). 7 It was reported that LIMK1 could increase breast cancer cells' metastasis via regulation of the urokinase-type plasminogen activator system, indicating that LIMK1 signaling played a major role in breast cancer in tumor growth, angiogenesis and motility.…”