The mitogen-activated protein kinase (MAPK) pathway is an important bridge in the switch from extracellular signals to intracellular responses. Alterations of signaling cascades are found in various diseases, including cancer, as a result of genetic and epigenetic changes. Numerous studies focused on both the homeostatic and the pathologic conduct of MAPK signaling; however, there is still much to be deciphered in terms of regulation and action models in both preclinical and clinical research. MAPK has implications in the response to cancer therapy, particularly the activation of the compensatory pathways in response to experimental MAPK inhibition. The present paper discusses new insights into MAPK as a complex cell signaling pathway with roles in the sustenance of cellular normal conduit, response to cancer therapy, and activation of compensatory pathways. Unfortunately, most MAPK inhibitors trigger resistance due to the activation of compensatory feed-back loops in tumor cells and tumor microenvironment components. Therefore, novel combinatorial therapies have to be implemented for cancer management in order to restrict the possibility of alternative pathway activation, as a perspective for developing novel therapies based on integration in translational studies.

Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The tumor is highly aggressive, the reason for which it has become the deadliest brain tumor type with the poorest prognosis. Like other cancers, it compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without the occurrence of any genetic mutations or DNA sequence alterations in the driver tumor-related genes. These epigenetic changes are reversible, making them convenient targets in cancer therapy. Therefore, we aim to review critical epigenetic dysregulation processes in glioblastoma. We will highlight the significant affected tumor-related pathways and their outcomes, such as regulation of cell cycle progression, cell growth, apoptosis, angiogenesis, cell invasiveness, immune evasion, or acquirement of drug resistance. Examples of molecular changes induced by epigenetic modifications, such as DNA epigenetic alterations, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) regulation, are highlighted. As understanding the role of epigenetic regulators and underlying molecular mechanisms in the overall pro-tumorigenic landscape of glioblastoma is essential, this literature study will provide valuable insights for establishing the prognostic or diagnostic value of various non-coding transcripts, including miRNAs.

Glioblastoma remains one of the most aggressive cancers of the brain, warranting new methods for early diagnosis and more efficient treatment options. Circular RNAs (circRNAs) are rather new entities with increased stability compared to their linear counterparts that interact with proteins and act as microRNA sponges, among other functions. Herein, we provide a critical overview of the recently described glioblastoma-related circRNAs in the literature, focusing on their roles on glioblastoma cancer cell proliferation, survival, migration, invasion and metastasis, metabolic reprogramming, and therapeutic resistance. The main roles of circRNAs in regulating cancer processes are due to their regulatory roles in essential oncogenic pathways, including MAPK, PI3K/AKT/mTOR, and Wnt, which are influenced by various circRNAs. The present work pictures the wide implication of circRNAs in glioblastoma, thus highlighting their potential as future biomarkers and therapeutic targets/agents.

Colon adenocarcinoma (COAD) remains an important cause of cancer-related mortality worldwide. Epithelial–mesenchymal transition (EMT) is a key mechanism, promoting not only the invasive or metastatic phenotype but also resistance to therapy. Using bioinformatics approaches, we studied the alteration on EMT related genes and its implication on COAD prognostic based on public datasets. For the EMT mechanisms, two overexpressed genes were identified (NOX4 and IGF2BP3), as well as five downregulated genes (BMP5, DACT3, EEF1A2, GCNT2 and SFRP1) that were related to prognosis in COAD. A qRT-PCR validation step was conducted in a COAD patient cohort comprising of 29 tumor tissues and 29 normal adjacent tissues, endorsing the expression level for BMP5, as well as for two of the miRNAs targeting key EMT related genes, revealing upregulation of miR-27a-5p and miR-146a-5p. The EMT signature can be used to develop a panel of biomarkers for recurrence prediction in COAD patients, which may contribute to the improvement of risk stratification for the patients.

(1) Background: Extrapulmonary tuberculosis (EPTB) of the head and neck is a rare but difficult diagnosis due to mostly absent pulmonary involvement and high clinical resemblance to neoplastic or chronic inflammatory conditions. This diagnosis still poses a challenge for otorhinolaryngologists, due to non-specific symptoms and the low index of suspicion in non-endemic regions. (2) Methods: This study presents a retrospective review of nine cases of head and neck EPTB diagnosed at two regional hospitals in southern Romania. Patients presented with pharyngeal, laryngeal, or cervical lymph node involvement. All cases underwent surgical biopsies for histopathological and microbiological confirmation, followed by standard anti-tubercular therapy. (3) Results: In all nine cases, surgical biopsies were essential for the accurate diagnosis and excluded malignancy or other granulomatous diseases. Diagnostic delays were observed due to atypical clinical presentations. Integration of biopsy findings with anti-tubercular treatment resulted in favorable disease control and clinical recovery. (4) Conclusions: Head and neck EPTB requires a high index of suspicion and clinical discernment. Surgical biopsy remains a critical diagnostic tool in practice and should be considered early in the diagnostic process when encountering atypical lesions. A timely use improves diagnostic accuracy, may eliminate delays, ensures patient safety, and improves therapeutic outcomes.

Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma.