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Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic–pituitary–adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a majority of patients presenting with unresectable or metastatic disease, resulting in a poor 5-year survival rate. This, in turn, is due to a highly complex tumor microenvironment and the presence of cancer stem cells, both of which induce therapy resistance and tumor relapse. Therefore, understanding and targeting the tumor microenvironment and cancer stem cells may be key strategies for designing effective PDAC therapies. In the present review, we summarized recent advances in the role of tumor microenvironment in pancreatic neoplastic progression.

Cancer stem cells are a cell population within malignant tumors that are characterized by the ability to self-renew, the presence of specific molecules that define their identity, the ability to form malignant tumors in vivo, resistance to drugs, and the ability to invade and migrate to other regions of the body. These characteristics are regulated by various molecules, such as lncRNAs, which are transcripts that generally do not code for proteins but regulate multiple biological processes through various mechanisms of action. LncRNAs, such as HOTAIR, H19, LncTCF7, LUCAT1, MALAT1, LINC00511, and FMR1-AS1, have been described as key regulators of stemness in cancer, allowing cancer cells to acquire this phenotype. It has been proposed that cancer stem cells are clinically responsible for the high recurrence rates after treatment and the high frequency of metastasis in malignant tumors, so understanding the mechanisms that regulate the stem phenotype could have an impact on the improvement of cancer treatments.

Breast cancer is the leading cause of cancer-related deaths in women worldwide. In the United States, even with earlier diagnosis and treatment improvements, the decline in mortality has stagnated in recent years. More research is needed to provide better diagnostic, prognostic, and therapeutic tools for these patients. Long non-coding RNAs are newly described molecules that have extensive roles in breast cancer. Emerging reports have shown that there is a strong link between these RNAs and the hypoxic response of breast cancer cells, which may be an important factor for enhanced tumoral progression. In this review, we summarize the role of hypoxia-associated lncRNAs in the classic cancer hallmarks, describing their effects on the upstream and downstream hypoxia signaling pathway and the use of them as diagnostic and prognostic tools.

(1) Aim: In the present paper we analyzed the transcriptome of CSCs (Cancer Stem Cells), in order to find defining molecular processes of breast cancer. (2) Methods: We performed RNA-Seq from CSCs isolated from the basal cell line MDA-MB-468. Enriched processes and networks were studied using the IPA (Ingenuity Pathway Analysis) tool. Validation was performed with qRT-PCR and the analysis of relevant genes was evaluated by overexpression, flow cytometry and in vivo zebrafish studies. Finally, the clinical relevance of these results was assessed using reported cohorts. (3) Results: We found that CSCs presented marked differences from the non-CSCs, including enrichment in transduction cascades related to stemness, cellular growth, proliferation and apoptosis. Interestingly, CSCs overexpressed a module of co-regulated Chromosomal Passenger Proteins including BIRC5 (survivin), INCENP and AURKB. Overexpression of BIRC5 increased the number of CSCs, as assessed by in vitro and in vivo zebrafish xenotransplant analyses. Analysis of previously published cohorts showed that this co-regulated module was not only overexpressed in basal breast tumors but also associated with relapse-free and overall survival in these patients. (4) Conclusions: These results underline the importance of Cancer Stem Cells in breast cancer progression and point toward the possible use of chromosomal passenger proteins as prognostic factors.