Vol 13, No 2 (2026)

Ferroptosis (FP), an iron-dependent form of regulated cell death driven by the accumulation of lipid peroxides and the impairment of antioxidant defenses, has recently emerged as a key pathophysiological mechanism in oncogenesis and aging. Concurrently, growing evidence indicates that age-associated alterations in hematopoietic stem cells, including the development of clonal hematopoiesis of indeterminate potential (CHIP), exert systemic effects on the formation of a pro-oncogenic microenvironment outside the bone marrow. This review evaluates the hypothesis that FP acts as a key selective mechanism (in aging hematopoiesis, driving the depletion of the normal hematopoietic stem cells pool while promoting the corresponding expansion of mutant clones with relative resistance to oxidative and iron-dependent stress.

We examine in detail the molecular mechanisms of FP (the SLC7A11–GSH–GPX4 axis, iron metabolism, lipid peroxidation, and the role of mitochondria), involutive shifts in the metabolic and redox status of hematopoietic stem cells, and their links to myeloid-biased differentiation and the inflammatory phenotype of CHIP clones. Special attention is dedicated to how macrophages and monocytes derived from FP-resistant clones sustain chronic, low-grade inflammation (inflammaging), impair antitumor immune surveillance, and shape a tissue stroma conducive to the initiation and progression of age-associated solid tumors. Based on clinical and experimental data, we discuss the pathogenetic link between CHIP and an elevated risk of lung, liver, pancreatic, and colorectal cancers. Furthermore, the role of disrupted iron homeostasis and lipid metabolism directly within the tumor microenvironment is analyzed. We propose the concept of FP as a “selection filter” in aging hematopoiesis that dictates the clonal selection of cells with pro-oncogenic properties. In conclusion, we evaluate the prospects of targeted modulation of FP and pro-inflammatory signaling pathways in distinct cell types as a novel strategy for the prevention and treatment of age-associated solid tumors.

Neuroblastoma is a malignant tumor found in children and characterized by exceptional heterogeneity and complex microenvironment which plays a key role in disease progression and response to therapy. The review summarizes the modern data on cell composition of neuroblastoma microenvironment and its effect on prognosis promoting formation of promising treatment strategies. Modulation of tumor microenvironment can become the key approach to development of effective targeted therapy and immunotherapy for various types of neuroblastoma.

In recent years, the study of cancer stem cells and their role in the development of resistance to antitumor therapy, the progression and recurrence of malignant neoplasms has become an important topic of research. Many experimental studies have shown that cancer stem cells may be responsible for the initiation and progression of prostate cancer. The development of castration-resistant prostate cancer is accompanied by changes in the activity of many signaling pathways, such as WNT/β-catenin, interleukin 6 /STAT3, ALDH1, Notch1 and Hedgehog which regulate the genes responsible for pluripotency, self-renewal, and differentiation, indicating the presence of stem-like cells in the tumor.

Introduction. Galectins are a family of β-galactoside-binding proteins involved in the regulation of cell adhesion, proliferation, apoptosis, and the immune response, playing a key role in carcinogenesis. Galectin-3 is the only chimeric protein of the galectin family, whose functional activity is determined by its ability to oligomerize. Increased expression of galectin-3 in tumor tissue and its high serum concentration are associated with colorectal cancer (CRC) progression. However, the clinical, morphological, and prognostic significance of serum galectin-3 levels in this disease remains poorly understood.

Aim. To analyze the association of galectin-3 levels in the blood serum of patients with key clinical, morphological characteristics and prognosis of CRC.

Materials and methods. A total of 210 previously untreated patients with CRC at various stages of the tumor were examined. These patients ranged in age from 31 to 75 years (114 men and 96 women). The control group consisted of 32 healthy donors aged 31 to 67 years (20 women and 12 men). The clinical diagnosis in all patients was confirmed by tumor morphological examination according to the International Histological Classification of Tumors of the Digestive Tract of the World Health Organization (2019). All patients were diagnosed with colon adenocarcinoma of varying degrees of differentiation. Galectin-3 concentrations were determined in serum collected using a standard method before the start of specific treatment using the Human Galectin-3 Quantikine ELISA reagents (R&D Systems, USA) according to the manufacturer’s instructions. Measurements were performed on a BEP 2000 Advance automated enzyme-linked immunosorbent assay (Siemens Healthcare Diagnostics, Germany). Marker levels were expressed as nanograms (ng) per 1 ml of serum. The nonparametric Mann–Whitney and Kruskal–Wallis tests were used to compare parameters and analyze their relationships. Overall survival was analyzed using the Kaplan–Meier method and the nonparametric Cox proportional hazards model. Differences and correlations were considered statistically significant at p < 0.05.

Results. Enzyme-linked immunosorbent assay revealed that baseline pre-treatment serum galectin-3 levels in 210 previously untreated CRC patients ranged widely from 2.6 to 24.7 ng / ml, and the median level (10.7 ng / ml) was statistically significantly higher than that in 32 healthy control donors (8.6 ng / ml) (p = 0.004). ROC analysis data do not support the use of serum galectin-3 levels in the diagnosis of CRC (test sensitivity 39 %, specificity 94 %). The study did not reveal any significant associations between galectin-3 levels and the main clinical and morphological characteristics of CRC. Univariate analysis and Cox regression analysis of galectin-3 levels revealed an unfavorable prognostic significance of this protein in patients with CRC (p = 0.0006 and p = 0.0001, respectively).

Conclusion. A statistically significant increase in serum galectin-3 concentrations was observed in patients with colorectal cancer compared to healthy donors. Despite the lack of associations with clinical and morphological characteristics of the tumor, elevated baseline serum galectin-3 levels in patients with colorectal cancer are significantly associated with a poor overall survival prognosis.

Introduction. The effectiveness of chemotherapy is determined by the percentage of tumor cells killed and the absence of tumor recurrence. The cell cycle regulator p21 plays a key role in these processes, although its role remains unclear.

Aim. To determine the effect of CDKN1A expression before and after exposure of tumor cells to doxorubicin on therapeutic efficacy.

Materials and methods. Flow cytometry was used for analysis of cell distribution per cell cycle phases, immunocytochemical staining was used for β-galactosidase activity measurement. Change in protein expression was evaluated using Western blot. For colony visualization, the cells were stained with crystal violet.

Results. It was found that overexpression of the p21 gene (CDKN1A) during cell exposure to doxorubicin reduces the number of cells that have stopped dividing in the G2/M phase of the cell cycle and increases their number in the G1 phase. This, in the absence of CDKN1A expression, subsequently leads to resumption of proliferation. Conversely, the absence of p21 during chemotherapy exposure results in a significant increase in the percentage of cells in the G2/M phase, followed by their death. Induction of CDKN1A expression after removal of doxorubicin, or throughout the experiment, leads to the development of a cellular senescence stage.

Conclusion. Increased CDKN1A expression during cell exposure to doxorubicin reduces its effectiveness. Maintaining high p21 levels after removal of the drug promotes the development of a cellular senescence phenotype.

Introduction. Histone methyltransferase NSD1 is often inactivated in head and neck squamous cell carcinoma. Loss of NSD1 is associated with improved prognosis in HPV (human papilloma virus) negative cancer. However, data on the signaling pathways regulated by NSD1 are limited.

Aim. Validation and systemic assessment of reproducibility of the NSD1-Akt/mTORC1 axis based on integrative analysis of open transcriptomic and proteomic data from cell lines and samples of head and neck squamous cell carcinoma.

Materials and methods. Systemic analysis was performed of the connection between NSD1 and Akt/mTORC1 signaling pathway using open transcriptomic and proteomic data (panel of squamous cell carcinoma cell lines on the DepMap portal and clinical cohorts from the The Cancer Genome Atlas (TCGA)). Pathway activity was evaluated using ssGSEA/GSEA (single-sample Gene Set Enrichment Analysis), proteomic activity – using protein expression data obtained with Reverse Phase Protein Array (RPPA), statistical significance – using standard correlation and nonparametric tests.

Results. In the cell line panel, elevated NSD1 expression correlated with stronger PI3K/AKT/mTOR transcription signature and increased phosphorylation of the key pathway components according to RPPA data. Similar correlation was observed in patient tumor samples. Data on isogenic cell lines with NSD1 knockout demonstrated decreased expression of mTORC1 target genes.

Conclusion. Reproducible correlation between NSD1 level and Akt/mTORC1 signaling pathway activity in head and neck cancer was established. However, additional confirmation of the NSD1 role in regulation of the Akt/mTORC1 pathways requires in vitro and in vivo investigation of expression and phosphorylation of protein components of this cascade, as well as functional experiments to evaluate proliferation, survival and drug sensitivity of head and neck cancer cells. Clinical significance of the established correlation in the context of disease progression requires further verification.