Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma characterized by poor prognosis and high rate of metastasis. Current treatment is based on chemo- and/or radiotherapy and surgery. TNBC is devoid of estrogen, progesterone and HER2 receptors. Although precision medicine has come a long way to ameliorate breast cancer disease management, targeted therapies for the treatment of TNBC patients are still limited. Mounting evidence has shown that non-coding RNAs (ncRNAs) drive many oncogenic processes at the basis of increased proliferation, invasion and angiogenesis in TNBC, strongly contributing to tumor progression and resistance to treatments. Many of these ncRNAs are secreted in the tumor microenvironment (TME) and impinge on the activity of the diverse immune and stromal cell types infiltrating the TME. Importantly, secreted ncRNAs may be detected as circulating molecules in serum/plasma from cancer patients and are emerging a promising diagnostic/therapeutic tools in TNBC. This review aims to discuss novel insights about the role of secreted circulating ncRNAs in the intercellular communication in the tumor microenvironment and their potential clinical use as diagnostic and prognostic non-invasive biomarkers in TNBC.
Highlights
Breast cancer is the second leading cause of cancer-related mortality in women
A cell type that is strongly reprogrammed in the tumor microenvironment (TME) of primary tumors and at metastatic sites is the cancer-associated fibroblast (CAF), which contributes to cancer progression through its ability to affect extracellular matrix composition, T-cell function and growth factors secretion
The identification and the full understanding of circulating non-coding RNAs (ncRNAs) roles in the TME could strongly help in assessing the risk of relapse and metastasis, the response to treatment and in developing new molecular targeted therapies to improve the survival in Triplenegative breast cancer (TNBC)
Summary
Breast cancer is the second leading cause of cancer-related mortality in women. Triplenegative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by significant inter- and intra-tumor molecular heterogeneity and defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 receptor. Extracellular vesicles containing a variety of macromolecules, included non-coding RNAs, are released in the tumor microenvironment (TME), where they actively participate in cancer progression (Figure 1). Non-tumor cell types in the tumor stroma may be targeted by cancer-derived EVs. A cell type that is strongly reprogrammed in the TME of primary tumors and at metastatic sites is the cancer-associated fibroblast (CAF), which contributes to cancer progression through its ability to affect extracellular matrix composition, T-cell function and growth factors secretion (reviewed in [33]). CRiNrcAuslactainngaRlsNo AsusrvcaivneailnsoexsturervmiveepiHn ceoxntrdeimtioenpsH, acsothnodsiteiopnres,seanstthinoesextprarecesellnutlairn eenxvtriarocenlmluelanrt,enanvdirotnhmis eennta, banleds tthhiesierndaebtleecstitohneirindeatevcatiroientyinoaf vbairoileotgyiocaf lbfliouloidgsic, aslufcluhidas, blood, urine, tears, cerebrospinal fluid, saliva, and semen [52] These features have made it possible to explore and develop liquid biopsy approaches for diagnosis purposes and to define the prognosis and therapeutic decisions in many tumor types, including TNBC. The identification and the full understanding of circulating ncRNA roles in the TME could strongly help in assessing the risk of relapse and metastasis, the response to treatment and in developing new molecular targeted therapies to improve the survival in TNBC
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