Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting BCSCs and expands on the challenges for the development of anti-BCSC drugs. We explore cutting-edge approaches like artificial intelligence (AI)-driven drug discovery and urge readers to seriously consider biological clocks and chronotherapy as experimental variables in drug discovery. Collectively, the task of cancer researchers is to overcome the many hurdles targeting BCSCs if we hope to tangibly improve breast cancer treatment outcomes and reduce mortality.

(1) Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders worldwide; its complex etiopathology remains poorly understood. PCOS is associated with a broad spectrum of abnormalities, including irregular menses, androgen excess, and increased risk of metabolic, endocrinological, and cardiovascular disorders. This narrative review focuses on structural and functional changes in the uterus associated with polycystic ovary syndrome and hyperandrogenism. (2) The review was performed by searching PubMed, Medline, Embase, Google Scholar, and Cochrane Library electronic databases on records published between 1964 and 2025. The authors included studies on (i) the uterus in clinical settings of PCOS patients, (ii) the uterus in PCOS models, and (iii) the pregnant uterus in patients with PCOS. Multiple animal and human studies describe a potential impact of PCOS on uterine blood flow, morphology, and thickness of the uterine muscle, indicating a possible functional impairment in pregnant and non-pregnant women. The scope of available knowledge regarding functional and structural uterine changes in PCOS is scarce; new studies are warranted. Future research should focus on hyperandrogenism associated with PCOS and explore the link between the morphology and function of the uterus.

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for Helicobacter pylori (H. pylori) or in advanced GC cases, F. nucleatum exerts diverse oncogenic effects. It promotes GC progression by modulating the tumor microenvironment through IL-17/NF-κB signaling, inducing tumor-associated neutrophils (TANs), upregulating PD-L1 expression, and enhancing immune evasion. Moreover, it increases tumor invasiveness via cytoskeletal reorganization, while extracellular vesicles (EVs) induced by the infection contribute to tumor cell proliferation, invasion, and migration. Clinically, its presence correlates with increased tumor mutational burden (TMB), venous thromboembolism, and poor prognosis. This review summarizes the current evidence regarding the emerging role of F. nucleatum in gastric tumorigenesis, examines its potential utility as a diagnostic and prognostic biomarker within the framework of precision oncology, and outlines the molecular methodologies presently employed for its detection in gastric tissue specimens.

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor in adults, characterized by high intratumoral heterogeneity, therapy resistance, and poor prognosis. Nuclear factor-κB (NF-κB) signaling plays a pivotal role in GBM pathogenesis by promoting proliferation, invasion, inflammation, immune evasion, and treatment resistance. This review provides a comprehensive overview of canonical and non-canonical NF-κB signaling pathways and their molecular mechanisms in GBM, with a focus on their regulation in glioma stem-like cells (GSCs), interactions with key oncogenic factors (including STAT3, FOSL1, and TRPM7), and roles in maintaining tumor stemness, metabolic adaptation, and angiogenesis. We further discuss the reciprocal regulatory dynamics between NF-κB and non-coding RNAs (ncRNAs), particularly microRNAs, highlighting novel ncRNA-mediated epigenetic switches that shape GBM cell plasticity and subtype specification. Additionally, we examine the influence of NF-κB in modulating the tumor microenvironment (TME), where it orchestrates pro-tumorigenic cytokine production, immune cell reprogramming, and stromal remodeling. Finally, we review current NF-κB-targeting therapeutic strategies in GBM, including clinical trial data on small-molecule inhibitors and combinatorial approaches. Understanding the multifaceted roles of NF-κB in GBM offers new insights into targeted therapies aimed at disrupting tumor-promoting circuits within both cancer cells and the TME.

CD20-negative aggressive B-cell lymphomas are a rare and heterogeneous group of lymphomas representing a diagnostic challenge for pathologists and a therapeutic issue for clinicians, because the outcome of these patients is poor with the current therapeutic approaches. CD20-negative aggressive lymphomas include plasmablastic lymphoma, primary effusion lymphoma, ALK-positive large B-cell lymphoma and HHV8-positive diffuse large B-cell lymphoma. Conditions of immunosuppression and viral infections, such as Epstein-Barr virus and Human Herpes virus 8, are associated with all of these lymphomas with the exclusion of ALK-positive large B-cell lymphoma, which occurs in immunocompetent hosts and is not associated with viral infections. Common features of these aggressive tumors are high-grade histology with immunoblastic or plasmablastic differentiation, the absence or weak expression of mature B-cell markers such as CD20 and the frequent expression of plasma cell-associated markers. The aim of this review is to highlight the diagnostic challenges associated with the group of CD20-negative aggressive B-cell lymphomas, emphasizing key morphologic and molecular features, which are critical in the diagnosis of the different entities belonging to this rare group of diseases.

Hepatocellular carcinoma (HCC) is the most common liver cancer, with poor survival rates in advanced stages due to late diagnosis, tumor heterogeneity, and therapy resistance. The tumor microenvironment (TME) in HCC has a crucial role in tumor progression, characterized by a complex interaction of immune cells, stromal components, and immunosuppressive signaling pathways. Chronic inflammation driven by viral infections, metabolic dysfunction, and alcohol consumption triggers an immunosuppressive TME, promoting immune evasion and tumor growth. Immune cell populations, such as myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages, contribute to immunosuppression, while cytotoxic T lymphocytes and natural killer cells exert anti-tumor effects. Recent advances in immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting programmed death-ligand 1 and programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4, have revolutionized HCC treatment, though response rates remain limited. Combined therapies using tyrosine kinase inhibitors, anti-angiogenic agents, and ICIs improve patient outcomes. This review discusses the immunological mechanisms contributing to HCC progression, the role of immune cell subsets in tumor evasion, and therapeutic interventions, from conventional treatments to advanced immunotherapies. Ongoing clinical trials, barriers to effective treatment, and future directions to enhance HCC management and patient survival will also be overviewed.

Cutaneous malignant melanoma remains one of the most aggressive forms of skin cancer, characterized by high metastatic potential and resistance to standard therapies. Emerging evidence suggests that transient receptor potential (TRP) channels, non-selective cation channels involved in calcium homeostasis, and cellular stress responses play a pivotal role in melanoma development and progression. This review highlights the physiological expression of key TRP subfamilies (TRPM1, TRPM7, TRPM8, TRPV1, TRPV4, and TRPM2) in melanocytes and discusses their dysregulation in melanoma cells. TRPM1 is implicated as a tumor suppressor, whereas TRPM7, TRPV1, and TRPV4 often function as both melanoma suppressor or oncogenic drivers, modulating proliferation, apoptosis, and metastasis. TRPM2, which is responsive to oxidative stress, supports melanoma cell survival under metabolic stress. The potential of TRP channels as diagnostic biomarkers and therapeutic targets is evaluated, with attention paid to current pharmacological approaches and research challenges. The complexity and context-dependency of TRP function in melanoma underscore the need for isoform-specific modulation and personalized therapeutic strategies.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a key regulator of cancer stem cell (CSC) biology and signaling. In CSCs, ROR1 acts as a receptor or co-receptor, interacting with non-canonical WNT ligands, and forming complexes with proteins like CD19 and HER2, to activate diverse downstream signaling pathways. ROR1 signaling in CSCs promotes proliferation, maintains stemness, and enhances migration, invasion, and the epithelial-to-mesenchymal transition (EMT). While minimally expressed after embryogenesis, ROR1 is aberrantly upregulated in numerous cancers, including ovarian, breast, pancreatic, and hematologic malignancies. ROR1 overexpression drives tumor progression, resistance to chemotherapies, disease recurrence, and ultimately metastasis. This expression pattern positions ROR1 as a promising target for CSC-specific therapies. High ROR1 expression is consistently linked to aggressive disease and poor patient outcomes. Here, we review ROR1's role in CSCs and highlight the complex signaling that is observed in the CSC population. Further, we evaluate the gaps in the current understanding of ROR1 signaling in CSCs and describe how ROR1 regulates the associated signaling pathways. Finally, we provide an up-to-date summary of the promising therapeutic strategies targeting ROR1 that overcome conventional cancer treatment limitations. This review highlights the role of ROR1 as a critical, functional driver of CSCs and adverse patient outcomes across various malignancies.

Pancreatic neuroendocrine tumors (pNETs) are rare malignancies, accounting for 1-2% of pancreatic cancers, with an incidence of ≤1 case per 100,000 individuals annually. Originating from pancreatic endocrine cells, pNETs display significant clinical and biological heterogeneity. Traditional classification based on proliferative grading does not fully capture the complex mechanisms involved, such as oxidative stress, mitochondrial dysfunction, and tumor-associated macrophage infiltration. Recent advances in molecular profiling have revealed key oncogenic drivers, including MEN1 (menin 1), DAXX (death domain-associated protein), ATRX (alpha thalassemia/mental retardation syndrome X-linked), CDKN1B (cyclin-dependent kinase inhibitor 1B) mutations, chromatin remodeling defects, and dysregulation of the mTOR pathway. Somatostatin receptors, particularly SSTR2, play a central role in tumor biology and serve as important prognostic markers, enabling the use of advanced diagnostic imaging (e.g., Gallium-68 DOTATATE PET/CT) and targeted therapies like somatostatin analogs and peptide receptor radionuclide therapy (PRRT). Established biomarkers such as Chromogranin A and the Ki-67 proliferation index remain vital for diagnosis and prognosis, while emerging markers, like circulating tumor DNA and microRNAs, show promise for enhancing disease monitoring and diagnostic accuracy. This review summarizes the molecular landscape of pNETs and highlights genomic, transcriptomic, proteomic, and epigenomic factors that support the identification of novel diagnostic, prognostic, and therapeutic biomarkers, ultimately advancing personalized treatment strategies.

Helicobacter pylori (H. pylori) infection and autoimmune inflammation of the gastric mucosa are recognized as the leading etiological factors of chronic atrophic gastritis. The mechanisms of atrophy formation and progression with the risk of gastric cancer development are heterogeneous, which requires a deeper study of the molecular mechanisms of relationship, peculiarities of the course of autoimmune gastritis both in combination with H. pylori and after eradication, as well as without H. pylori infection (naïve AIG). This article presents the specific molecular and cellular patterns in the formation of these related conditions.

The exposure to risk factors, such as cigarette smoke and air pollution (containing metabolic oxidants and toxic substances), leading to cellular and molecular alterations, promotes the development of lung cancer at multiple stages. The antioxidant defence system plays a critical role in counteracting the mechanisms of oxidative stress. In physiological conditions, the balance between pro-oxidant and antioxidant species is critically important for the correct performance of cellular functions. Its imbalance is accompanied by the onset and progression of various pathologic states, including lung cancer. Cell signalling pathways and non-coding RNAs play a crucial role in the mechanisms of carcinogenesis and in the development of resistance to conventional therapeutic treatments. The interplay between the oxidant/antioxidant system, transcription factors, and non-coding RNAs is involved in the development and in the pathogenesis of lung cancer. This review provides a comprehensive resource for researchers and clinicians to better understand this intricate system and its cellular interactions, with the aim of disseminating the knowledge of the mechanisms involved in both cancer development and the development of new anti-cancer therapeutic strategies. A thorough understanding of the interplay between oxidative stress mechanisms, the activity of transcription factors, and non-coding RNAs could improve the efficacy of drug treatments and open new pharmacological perspectives for the control of inflammation and disease progression in lung cancer.

Breast cancer (BC) remains one of the most prevalent and life-threatening malignancies worldwide, marked by significant heterogeneity and complex mechanisms of progression. Despite major advances in understanding its molecular and cellular basis, the processes driving tumor progression and metastasis continue to challenge effective treatment. Among the emerging research areas, extracellular vesicles (EVs) have gained considerable attention for their key role in intercellular communication and their contribution to cancer biology. In BC, tumor cell-derived EVs are implicated in multiple processes that promote disease progression, including tumor growth, remodeling of the tumor microenvironment, and facilitation of metastasis. By transferring oncogenic signals to recipient cells, EVs critically shape the metastatic niche and support the spread of cancer cells to distant organs. Recent studies highlight the diverse functions of BC-derived EVs in modulating immune responses, inducing angiogenesis, and enhancing cancer cell invasiveness. This review explores the role of BC-derived EVs in tumor progression and metastasis. We discuss their molecular composition, mechanisms of action, and impact on the tumor microenvironment, aiming to provide insights into their role in BC pathophysiology and discuss potential clinical applications. A deeper understanding of the complex interplay between EVs and cancer progression may pave the way for innovative strategies to combat BC and improve patient outcomes.

Helminths that inhabit the gastrointestinal (GI) tract represent some of the most significant infectious agents impacting health. The interaction between the human microbiota, GI helminths, and their host occurs through multiple complex pathways, altering the host's immune system and the dynamics of the commensal gut microbiota (GM). These interactions also largely influence a balanced state of homeostasis and health promotion and robustly activate the immune system, facilitating tumor eradication and mitigating the challenges of drug resistance. Furthermore, incorporating microbial metabolites into radiotherapy and chemotherapy reduces the intense adverse effects of these treatments while enhancing their overall effectiveness. The interplay between GM and helminths, as well as their metabolites, significantly impacts the development, prognosis, and treatment of cancer. The interaction mechanisms between GI helminths and the GM are not fully elucidated. Thus, understanding a beneficial biological relationship can reveal hidden mechanisms for controlling and inhibiting cancer pathways in humans by providing insights into cellular processes and potential therapeutic targets. This knowledge can be applied to develop more effective cancer treatments. This review outlines the existing research on GM metabolites in cancer, intending to offer innovative pathways for future cancer treatment.

(1) Background: The gold standard, prostate-specific antigen (PSA) screening lacks the sensitivity and specificity required for confident, early prostate-cancer detection. MicroRNAs (miRNAs) are small, highly stable, non-coding RNAs whose expression changes reproducibly in malignancy and therefore offer promise as minimally invasive biomarkers. Although prostate cancer biopsies are the gold standard for prostate cancer diagnosis, limitations in the field continue to persist. Since circulating fluids can also be a source of miRNA biomarkers, we investigated the overlap between miRNAs enriched in prostate cancer tissue and those isolated from the plasma of patients with prostate cancer. (2) Methods: We synthesized the published literature (PubMed, Google Scholar, ResearchGate, 2005-April 2025) and re-analyzed three Gene Expression Omnibus (GEO) datasets (GSE54516, GSE21032-tissue; GSE206793-plasma) to identify miRNAs consistently dysregulated in prostate cancer tissue and circulation. (3) Results: Of the 318 screened full-text articles, 24 met the inclusion criteria. From the GEO reanalysis (false-discovery-rate < 0.05, |log2FC| ≥ 1), 219 and 326 miRNAs were differentially expressed in tissue, whereas 12 were altered in plasma. Two miRNAs-miR-449b and miR-455-3p-were common in both compartments, highlighting their translational potential as liquid biopsy surrogates of tumor biology. (4) Conclusions: We summarize functional evidence for leading tumor-suppressive (e.g., miR-205, miR-23b, miR-455-3p) and oncogenic (e.g., miR-21, miR-182, miR-449b) candidates, discuss their intersection with the androgen-receptor, TGF-β, WNT/β-catenin, and PI3K-AKT signaling, and outline outstanding requirements for the clinical qualification of miRNA panels in prostate cancer.

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.

Colorectal cancer (CRC) is not only the third most common cancer worldwide, with 1.1 million new cases per year; it is also the second leading cause of cancer death. However, mortality has decreased since 2012 due to early detection programs and better therapeutic approaches. While many patients are diagnosed at an early stage, there is up to 50% relapse after optimal initial treatment. Therefore, it is crucial to explore the mechanism underlying the development of recurrences and metastasis. It is known that tumors release dormant cells that escape chemotherapy and nest in a target organ without proliferating. Under certain circumstances that are not yet entirely clear, they can be activated and metastasize. Therefore, the objective of this work is to explore the detailed mechanisms of dormancy, including early detection of recurrence and therapeutic approaches for the treatment of CRC. The specific objectives are to determine biomarkers that may be useful in identifying dormant cells to detect minimal residual disease (MRD) after surgery and predicting disease progression, as well as evaluating biomarkers that are susceptible to therapeutic intervention.

MicroRNA-211 (miR-211) is a versatile regulatory molecule that plays critical roles in cellular homeostasis and disease progression through the post-transcriptional regulation of gene expression. This review comprehensively examines miR-211's multifaceted functions across various biological systems, highlighting its context-dependent activity as both a tumor suppressor and oncogene. In physiological contexts, miR-211 regulates cell cycle progression, metabolism, and differentiation through the modulation of key signaling pathways, including TGF-β/SMAD and PI3K/AKT. miR-211 participates in retinal development, bone physiology, and protection against renal ischemia-reperfusion injury. In pathological conditions, miR-211 expression is altered in various diseases, particularly cancer, where it may be a useful diagnostic and prognostic biomarker. Its stability in serum and differential expression in various cancer types make it a promising candidate for non-invasive diagnostics. The review also explores miR-211's therapeutic potential, discussing both challenges and opportunities in developing miRNA-based treatments. Understanding miR-211's complex regulatory interactions and context-dependent functions is crucial for advancing its clinical applications for diagnosis, prognosis, and targeted therapy in multiple diseases.

Tumor drug resistance, a major cause of treatment failure, involves complex multi-gene networks, remodeling of signaling pathways, and interactions with the tumor microenvironment. Yin Yang 1 (YY1) is a critical oncogene overexpressed in many tumors and mediates multiple tumor-related processes, such as cell proliferation, metabolic reprogramming, immune evasion, and drug resistance. Notably, YY1 drives resistance through multiple mechanisms, such as upregulation of drug efflux, maintenance of cancer stemness, enhancement of DNA repair capacity, modulation of the tumor microenvironment, and epithelial-mesenchymal transition, thereby positioning it as a pivotal regulator of drug resistance. This review examines the pivotal role of YY1 in resistance, elucidating its molecular mechanisms and clinical relevance. We demonstrate that YY1 inhibition could effectively reverse drug resistance and restore therapeutic sensitivity across various treatment modalities. Importantly, we highlight the promising potential of YY1-targeted strategies, particularly combined with anti-tumor agents, to overcome resistance barriers. Furthermore, we discuss critical translational considerations for advancing these combinatorial approaches into clinical practice.

Breast cancer, the most prevalent malignancy among women worldwide, exhibits significant heterogeneity, particularly in the tumor microenvironment (TME), which poses challenges for treatment. Spatial transcriptomics (ST) has emerged as a transformative technology, enabling gene expression analysis while preserving tissue spatial architecture. This provides unprecedented insights into tumor heterogeneity, cellular interactions, and disease mechanisms, offering a powerful tool for advancing breast cancer research and therapy. This review aims to synthesize the applications of ST in breast cancer research, focusing on its role in decoding tumor heterogeneity, characterizing the TME, elucidating progression and metastasis dynamics, and predicting therapeutic responses. We also explore how ST can bridge molecular profiling with clinical translation to enhance precision therapy. The key scientific concepts of review included the following: We summarize the technological advancements in ST, including imaging-based and sequencing-based methods, and their applications in breast cancer. Key findings highlight how ST resolves spatial heterogeneity across molecular subtypes and histological variants. ST reveals the dynamic interplay between tumor cells, immune cells, and stromal components, uncovering mechanisms of immune evasion, metabolic reprogramming, and therapeutic resistance. Additionally, ST identifies spatial prognostic markers and predicts responses to chemotherapy, targeted therapy, and immunotherapy. We propose that ST serves as a hub for integrating multi-omics data, offering a roadmap for precision oncology and personalized treatment strategies in breast cancer.

Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.