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Simple Summary: Triple-negative breast cancer (TNBC) is a challenging-to-treat breast cancer subtype, characterized by high recurrence, increased risk of metastasis, and lower survival for patients compared to other breast cancer subtypes. Depending on the clinical advancement of the disease, surgery, radiotherapy, and chemotherapy remain the standard treatment, though they often have limited long-term efficacy. Chemoresistance in TNBC is closely related to the epithelial–mesenchymal transition (EMT), a process where tumor cells gain mesenchymal-like characteristics. This, in turn, increases their metastatic potential and resistance to standard chemotherapeutic treatments. There is a growing interest in small-molecule inhibitors targeting EMT as a potential strategy to overcome resistance and improve TNBC patient outcomes. This review discusses the TNBC progression and drug resistance within the context of EMT, highlighting molecular features, key EMT protein markers, and signaling pathways. It also explores other mechanisms and factors related to chemoresistance in TNBC with an emphasis on treatment advancements. Triple-negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat due to its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk of metastasis, and lower overall survival compared to other breast cancer subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds and taxanes) continues to be the standard treatment for TNBC, often with limited long-term efficacy. TNBC tumors are heterogeneous, displaying a diverse mutation profile and considerable chromosomal instability, which complicates therapeutic interventions. The development of chemoresistance in TNBC is frequently associated with the process of epithelial–mesenchymal transition (EMT), during which epithelial tumor cells acquire a mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing the effectiveness of standard chemotherapeutics. It has also been suggested that EMT plays a central role in the development of cancer stem cells. Hence, there is growing interest in exploring small-molecule inhibitors that target the EMT process as a future strategy for overcoming resistance and improving outcomes for patients with TNBC. This review focuses on the progression and drug resistance of TNBC with an emphasis on the role of EMT in these processes. We present TNBC-specific and EMT-related molecular features, key EMT protein markers, and various signaling pathways involved. We also discuss other important mechanisms and factors related to chemoresistance in TNBC within the context of EMT, highlighting treatment advancements to improve patients' outcomes. [ABSTRACT FROM AUTHOR]

Cancer is a multifactorial disease resulting from both genetic factors and epigenetic changes. Histone acetylation, a post-translational modification, which alters chromatin architecture and regulates gene expression is associated with cancer initiation, development and progression. Aberrations in global histone acetylation levels are observed in various cancer cells and are also associated with patients' tumor aggressiveness. Therefore, histone acetylation may have prognostic utility and serve as a potential biomarker of cancer progression and patients' prognosis. The reversible modification of histones by an acetyl group is versatile. One particular histone can be acetylated on different lysine residues, subsequently resulting in different biological outcomes. Here, we discuss recent findings on the acetylation of the highly conserved histone protein H3 in the context of cancer biology. Specifically, we review the acetylation of particular H3 residues in various cancer types. We further highlight the significance of H3 acetylation levels as a potential cancer biomarker with prognostic implications. [ABSTRACT FROM AUTHOR]

SIRT6 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, predominantly located in the nucleus, that is involved in the processes of histone modification, DNA repair, cell cycle regulation, and apoptosis. Disturbances in SIRT6 expression levels have been observed in the development and progression of various types of cancer. Therefore, it is important to better understand the role of SIRT6 in biochemical pathways and assign it specific biological functions. This review aims to summarize the role of SIRT6 in carcinogenesis and tumor development. A better understanding of the factors influencing SIRT6 expression and its biological role in carcinogenesis may help to develop novel anti-cancer therapeutic strategies. Moreover, we discuss the anti-cancer effects and mechanism of action of small molecule SIRT6 modulators (both activators and inhibitors) in different types of cancer. [ABSTRACT FROM AUTHOR]

In recent years, drug-resistant and multidrug-resistant fungal strains have been more frequently isolated in clinical practice. This phenomenon is responsible for difficulties in the treatment of infections. Therefore, the development of new antifungal drugs is an extremely important challenge. Combinations of selected 1,3,4-thiadiazole derivatives with amphotericin B showing strong synergic antifungal interactions are promising candidates for such formulas. In the study, microbiological, cytochemical, and molecular spectroscopy methods were used to investigate the antifungal synergy mechanisms associated with the aforementioned combinations. The present results indicate that two derivatives, i.e., C1 and NTBD, demonstrate strong synergistic interactions with AmB against some Candida species. The ATR-FTIR analysis showed that yeasts treated with the C1 + AmB and NTBD + AmB compositions, compared with those treated with single compounds, exhibited more pronounced abnormalities in the biomolecular content, suggesting that the main mechanism of the synergistic antifungal activity of the compounds is related to a disturbance in cell wall integrity. The analysis of the electron absorption and fluorescence spectra revealed that the biophysical mechanism underlying the observed synergy is associated with disaggregation of AmB molecules induced by the 1,3,4-thiadiazole derivatives. Such observations suggest the possibility of the successful application of thiadiazole derivatives combined with AmB in the therapy of fungal infections. [ABSTRACT FROM AUTHOR]

Glutamate antagonists limit the growth of human cancers in vitro. The mechanism of anticancer action of NMDA antagonists is not known, however. In this article, we report that the NMDA antagonist dizocilpine inhibits the extracellular signal-regulated kinase 1/2 pathway, an intracellular signaling cascade that is activated by growth factors and controls the proliferation of cancer cells. Dizocilpine reduces the phosphorylation of cAMP-responsive element binding protein, suppresses the expression of cyclin D1, up-regulates the cell cycle regulators and tumor suppressor proteins p21 and p53, and increases the number of lung adenocarcinoma cells in the [G.sub.2] and S phases of the cell cycle. Silencing of the tumor suppressor protein p21 abolishes antiproliferative action of dizocilpine. Consistent with inhibition of the extracellular signal-regulated kinase 1/2-signaling cascade, dizocilpine reverses the stimulation of proliferation induced by epidermal, insulin, and basic fibroblast growth factors in lung adenocarcinoma cells. Furthermore, dizocilpine prolongs the survival of mice with metastatic lung adenocarcinoma and slows the growth of neuroblastoma and rhabdomyosarcoma in mice. These findings reveal the mechanism of antiproliferative action of dizocilpine and indicate that it may be useful in the therapy of human cancers. cell cycle | growth factors | lung cancer | signal transduction