Search Results (2,204)

Breast cancer, a leading global malignancy, exhibits extensive metabolic reprogramming that drives tumorigenesis, therapy resistance, and survival. Ferroptosis, an iron-dependent regulated cell death mechanism characterized by lipid peroxidation, emerges as a promising therapeutic vulnerability, particularly in aggressive subtypes like triple-negative breast cancer (TNBC). This literature review comprehensively explores the metabolic regulation of ferroptosis in breast cancer cells, focusing on how dysregulated pathways modulate sensitivity or resistance. The review will discuss iron homeostasis, including upregulated transferrin receptor 1 (TFR1), diminished ferroportin, mitochondrial dynamics, and ferritinophagy, which catalyze ROS via Fenton reactions. It will examine glutathione (GSH) metabolism through the GPX4-GSH axis, with subtype-specific reliance on cystine import via xCT or de novo cysteine synthesis. Lipid metabolism will be analyzed as the core battleground, highlighting polyunsaturated fatty acid (PUFA) incorporation by ACSL4 promoting peroxidation, contrasted with monounsaturated fatty acid (MUFA) protection via SCD1, alongside subtype adaptations. Further, the review will address tumor microenvironment influences, such as cysteine supply from cancer-associated fibroblasts and oleic acid from adipocytes. Oncogenic signaling (e.g., RAS, mTOR) and tumor suppressors (e.g., p53) will be evaluated for their roles in resistance or sensitivity. Intersections with glucose metabolism (Warburg effect) and selenium-dependent antioxidants will be explored. Therapeutically, the review will consider targeting these nodes with GPX4 inhibitors or iron overload, synergized with immunotherapy for immunogenic cell death. Future directions will emphasize multi-omics integration and patient-derived organoids to uncover subtype-specific strategies for precision medicine in breast cancer. Full article

Erica spiculifolia Salisb. (Balkan heath) is an evergreen shrub growing in the mountain shrublands of Eastern Europe. E. spiculifolia was used as a diuretic, anti-inflammatory, and antioxidant herbal remedy. The present study aims to conduct an evaluation of the phytochemical composition and antitumor activity of the methanol–aqueous extract from E. spiculifolia aerial parts to explore its potential in cancer treatment. Overall, a total of 54 secondary metabolites, including 28 hydroxybenzoic, hydroxycinnamic acids, and phenolic glycosides, and 10 triterpene acids, together with 17 flavonoids, were identified or annotated in the assayed E. spiculifolia extract using liquid chromatography-high-resolution mass spectrometry. The cytotoxic activity of the extract, alongside gallic, protocatechuic, and oleanolic acids as its constituents, was screened against a panel of malignant human cell lines of different origin (LAMA-84, HL-60, MDA-MB-231, MCF-7, and CASKI). The most prominent antiproliferative effect of the studied extract (with IC₅₀ 16.6 μg/mL), matched with the highest tumor selectivity (SI > 120), was observed in the LAMA-84 myeloid cells. These findings were further supported by gallic and oleanolic acid (IC₅₀ 6.2 and 1.7 μg/mL, respectively), accounting for a more distinct cytotoxicity. The strongest selective antineoplastic activity was achieved towards the triple-negative breast carcinoma cell line MDA-MB-231, with an IC₅₀ of 32.5 μg/mL. This study provided compelling evidence for a wide spectrum of E. spiculifolia antitumor activity, indicating its potential as a natural alternative for future therapeutic applications. Full article

Microwave Breast Imaging (MWBI) is an emerging imaging modality aiming to detect breast lesions, which are dielectrically contrasted against the background healthy tissue, in the microwave frequency spectrum. MWBI holds potential to outperform X-ray mammography’s low sensitivity in young and dense breasts, thus supporting timelier detection of interval cancers, as a supplemental screening or diagnostic imaging method. The specificity of MWBI remains unknown, however, as management of false positives has not been systematically addressed yet. An earlier First-In-Human clinical investigation on 24 symptomatic patients provided proof-of-concept for the Wavelia MWBI sectorized multi-static radar imaging technology, which generates clinically meaningful 3D images of the breast, performs semi-automated detection of breast lesions and extracts diagnostic features to distinguish malignant from benign lesions. This paper focuses on a set of technological upgrades, accessories and data processing modules, designed and implemented in the 2nd generation prototype of Wavelia, to handle the diversity in breast geometry, tissue consistency and deformability, in a larger clinical investigation reporting on the bilateral MWBI scan of 62 patients. The presented add-on modules contribute to enhanced quality of scan and a more valid reference reporting space for the MWBI imaging outputs, with a direct positive impact on overall specificity. Full article

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions. Full article

Phyllodes tumors are rare fibroepithelial neoplasms of the breast, and their malignant forms present significant diagnostic and therapeutic challenges. This review summarizes current knowledge across the benign-to-malignant spectrum, focusing on diagnostic approaches, histopathological classification, molecular alterations, and treatment strategies. While recent molecular studies have revealed recurrent genetic mutations, their clinical implications remain under investigation. Surgical excision remains the cornerstone of treatment, and systemic therapies are generally adapted from soft tissue sarcoma protocols. Future efforts should focus on improving diagnostic accuracy, identifying molecular targets for therapy, and fostering international collaboration to advance clinical research in this rare tumor type. Full article

Breast cancer is one of the major health threats to women worldwide; thus, a need has arisen to reduce the number of instances and deaths through new methods of diagnostic monitoring and treatment. The present review is the synthesis of the recent clinical studies and technological advances in the application of magnetic resonance imaging (MRI) to monitor the pharmacological treatment of breast cancer. The specific focus is on high-risk groups (carriers of BRCA mutations and recipients of neoadjuvant chemotherapy) and the use of novel MRI methods (dynamic contrast-enhanced (DCE) MRI, diffusion-weighted imaging (DWI), and radiomics tools). All the reviewed studies show that MRI is more sensitive (up to 95%) and specific than conventional imaging in detecting malignancy particularly in dense breast tissue. Moreover, MRI can be used to assess the response and residual disease in a tumor early and accurately for personalized treatment, de-escalate unneeded interventions, and maximize positive outcomes. AI-based radiomics combined with deep-learning models also expand the ability to predict the therapeutic response and molecular subtypes, and can mitigate the risk of overfitting models when using complex methods of modeling. Other developments are hybrid PET/MRI, image guidance during surgery, margin assessment intraoperatively, three-dimensional surgical templates, and the utilization of MRI in surgery planning and reducing reoperation. Although economic factors will always play a role, the diagnostic and prognostic accuracy and capability to aid in targeted treatment makes MRI a key tool for modern breast cancer. The growing complement of MRI and novel curative approaches indicate that breast cancer patients may experience better survival and recuperation, fewer recurrences, and a better quality of life. Full article

Breast cancer detection remains a significant challenge, with traditional mammography presenting barriers such as discomfort, radiation exposure, high false-positive rates, and financial burden. Moreover, younger women frequently fall outside routine mammographic screening guidelines, leaving critical gaps in early detection. Objectives: This study investigates the potential of quantitative transmission breast acoustic computed tomography scanner imaging (QT3D) as an innovative, non-invasive imaging modality for characterizing and evaluating breast masses. Methods: A comparative analysis between QT3D imaging and magnetic resonance imaging (MRI) was conducted in a cohort of patients with biopsy-proven benign or malignant breast lesions, comparing key metrics in quantifying breast masses for the purposes of breast mass characterization. Results: The findings in this study highlight its capability in identifying relatively small tumors, multiple lesions, satellite lesions, intraductal extensions, and calcifications, in addition to offering valuable diagnostic insights. Conclusions: This work is a first step toward studies essential for confirming its clinical feasibility, establishing its role in breast cancer tumor characterization, and potentially improving patient outcomes. Full article

Breast cancer (BC) is the most frequently diagnosed malignancy in women. Currently, BC is treated with a holistic and multidisciplinary approach from diagnostic, surgical, radio-oncological, and medical perspectives, and advances including in early detection and treatment methods have led to improved outcomes for patients in recent years. Yet, BC remains the second most common cause of cancer-related deaths among women and there is an array of gaps to achieve optimal care. To close gaps in cancer care, here we describe a collaborative Request For Proposals (RFP) framework supporting independent initiatives for metastatic breast cancer (MBC) patients and aiming at improving their quality of care. We set up a collaborative framework between Pfizer and Sharing Progress in Cancer Care (SPCC). Our model is based on an RFP system in which Pfizer and SPCC worked together ensuring the independence of the funded projects. We developed a three-step life cycle RFP. The collaborating framework of the project was based on an RFP with a USD 1.5 million available budget for funding independent grants made available from Pfizer and managed in terms of awareness, selection, and monitoring by SPCC. Our three-step model could be applicable and scalable to quality improvement (QI) initiatives that are devoted to tackling obstacles to reaching optimal care. Through this model, seven projects from five different European countries were supported. These projects covered a range of issues related to the experience of patients with MBC: investigator communication, information, and shared decision-making (SDM) practices across Europe; development, delivery, and evaluation of a scalable online educational program for nurses; assessment of disparities among different minority patient groups; development of solutions to improve compliance or adherence to therapy; an information technology (IT) solution to improve quality of life (QoL) of patients with MBC and an initiative to increase awareness and visibility of MBC patients. Overall, an average of 171 healthcare professionals (HCPs) per project and approximately 228,675 patients per project were impacted. We set up and describe a partnership model among different stakeholders within the healthcare ecosystem―academia, non-profit organizations, oncologists, and pharmaceutical companies―aiming at supporting independent projects to close gaps in the care of patients with MBC. By removing barriers at different layers, these projects contributed to the achievement of optimal care for patients with MBC. Full article

Breast cancer is the most common malignancy and leading cause of cancer-related mortality among women worldwide. Oestrogen receptor (ER)-positive disease accounts for the majority of cases, where endocrine and targeted therapies have substantially improved survival. Nevertheless, resistance to therapy remains inevitable, emphasising the need for precision strategies informed by molecular profiling. The molecular landscape of ER-positive breast cancer is increasingly complex, characterised by diverse genomic alterations driving resistance and progression. Advances in next-generation sequencing and circulating tumour DNA (ctDNA) technologies enable the dynamic assessment of tumour heterogeneity and clonal evolution, informing prognostication and guiding biomarker-driven therapy. Uniquely, this review integrates molecular phenotyping with clinical treatment algorithms for advanced ER-positive breast cancer, providing a practical framework to translate genomic insights into patient care. Key genomic alterations and targeted strategies with demonstrated clinical benefit, including oral selective ER degraders (SERDs) and PI3K/AKT/mTOR inhibitors in selected biomarker populations, are highlighted. Emerging targets, such as human epidermal growth factor 2 (HER2) mutations, and the potential of ctDNA monitoring to detect resistance and guide therapeutic escalation are also discussed. Incorporating molecular profiling, as recommended by international guidelines, into routine clinical decision making can personalise therapy and optimise patient outcomes. Addressing real-world challenges, including cost and accessibility, will be critical to achieving equitable implementation of precision oncology for patients with ER-positive breast cancer worldwide. Full article

Background: Breast cancer remains the most prevalent malignancy in women worldwide, characterized by remarkable genetic, molecular, and clinical heterogeneity. Traditional preclinical models have significantly advanced our understanding of tumor biology, yet consistently fall short in recapitulating the complexity of the human tumor microenvironment (TME), immune, and metastatic behavior. In recent years, breast cancer-on-a-chip (BCOC) have emerged as powerful microengineered systems that integrate patient-derived cells, stromal and immune components, and physiological stimuli such as perfusion, hypoxia, and acidic milieu within controlled three-dimensional microenvironments. Aim: To comprehensively review the BCOC development and application, encompassing fabrication materials, biological modeling of key subtypes (DCIS, luminal A, triple-negative), dynamic tumor–stroma–immune crosstalk, and organotropic metastasis to bone, liver, brain, lungs, and lymph nodes. Methods: We selected papers from academic trusted databases (PubMed, Web of Science, Google Scholar) by using Breast Cancer, Microfluidic System, and Breast Cancer on a Chip as the main search terms. Results: We critically discuss and highlight how microfluidic systems replicate essential features of disease progression—such as epithelial-to-mesenchymal transition, vascular invasion, immune evasion, and therapy resistance—with unprecedented physiological relevance. Special attention has been paid to the integration of liquid biopsy technologies within microfluidic platforms for non-invasive, real-time analysis of circulating tumor cells, cell-free nucleic acids, and exosomes. Conclusions: In light of regulatory momentum toward reducing animal use in drug development, BCOC platforms stand at the forefront of a new era in precision oncology. By bridging biological fidelity with engineering innovation, these systems hold immense potential to transform cancer research, therapy screening, and personalized medicine. Full article

Reprogramming is a hallmark of cancer, enabling tumour cells to sustain rapid proliferation, resist cell death, and adapt to hostile microenvironments. This review explores the expression profiles of key metabolic enzymes and transporters involved in glucose, amino acid, and lipid metabolism across the five most deadly cancers worldwide: lung, breast, colorectal, liver, and gastric cancers. Through a comparative analysis, we identify consistent upregulation of glycolytic enzymes such as LDHA, PKM2, and HK2, as well as nutrient transporters like GLUT1, ASCT2, and LAT1, which contribute to cancer progression, metastasis, and therapy resistance. The role of enzymes involved in glutaminolysis (e.g., GLS1, GDH), one-carbon metabolism (e.g., SHMT2, PHGDH), and fatty acid synthesis (e.g., FASN, ACLY) is also examined, with emphasis on their emerging relevance as diagnostic, prognostic, and predictive biomarkers. While several metabolic proteins show strong potential for clinical translation, only a few, such as tumour M2-pyruvate kinase (TuM2-PK) and serum LDH measurement, have progressed into clinical use or trials. This review addresses some of the challenges in biomarker development. Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology. Full article

Background: Breast cancer remains a predominant malignancy among females globally, and the tumor microenvironment (TME) exerts a pivotal role in its progression. Despite notable advancements in diagnostic and therapeutic modalities, resistance to conventional therapies persists as a critical hurdle, underscoring the necessity of exploring TME-related prognostic biomarkers. Methods: To elucidate the role of the TME in breast cancer progression and identify potential prognostic biomarkers, we analyzed RNA-seq data from 1081 breast cancer cases and 99 normal controls to assess tumor-infiltrating immune cells (TICs) and stromal components. Differential gene expression analysis identified genes correlated with ImmuneScore and StromalScore. A protein–protein interaction (PPI) network was constructed, followed by univariate Cox regression to pinpoint survival-associated genes. JCHAIN, significantly linked to survival outcomes, was selected for further investigation. Gene Set Enrichment Analysis (GSEA) and TIC correlation analyses were performed to explore its associations with immune pathways. Additionally, immunohistochemistry (IHC) and multiplexed immunofluorescence (mIF) were performed on 61 clinical samples. Results: High ImmuneScore was associated with improved survival. Joining chain of multimeric IgA and IgM (JCHAIN) expression was notably reduced in tumor tissues, with low expression correlating with poorer prognosis. GSEA highlighted immune-related pathways enriched in high JCHAIN expression groups. TIC analysis revealed positive correlations with CD8+ T cells and M1 macrophages. IHC and mIF validations further confirmed decreased JCHAIN protein expression in tumor tissues, and higher JCHAIN expression was associated with increased M1 macrophage density. Conclusions: JCHAIN serves as a promising prognostic biomarker in breast cancer, reflecting immune activity within the TME, providing valuable insights into immune-stromal interactions and the therapeutic potential of JCHAIN. Full article

Background: The ESR2 gene encodes Estrogen Receptor-β1 (ERβ1), a putative tumor suppressor in hormone-dependent malignancies. Although ERβ biology has been studied extensively at the expression level, the functional impact of nonsynonymous SNPs (nsSNPs) and untranslated-region (UTR) variants in ESR2 remains underexplored. Methods: We retrieved variants from Ensembl and performed an integrative in silico assessment using PredictSNP, I-Mutant, MUpro, HOPE, MutPred2, and CScape for pathogenicity, oncogenicity and structural stability; STRING/KEGG/GO for pathway context; RegulomeDB and polymiRTS for regulatory effects; and cBioPortal for pan-cancer clinical outcomes (breast (BRCA), endometrial (UCEC), and ovarian (OV)). We evaluated effects of nsSNPs on ERβ1 stability, ligand-binding/DNA-binding domains, co-factor recruitment, and post-transcriptional regulation. Results: Across tools, 93 missense nsSNPs were consistently predicted to be deleterious. Notably, several variants were found to destabilize ERβ1, particularly within the ligand-binding domains (LBD) and DNA-binding domains (DBD). Putative oncogenic drivers R198P and D154N showed high CScape scores and very low population frequencies, consistent with pathogenicity. Several substitutions were predicted to impair coactivator binding and disrupt interactions with key transcriptional partners, including JUN, NCOA1, and SP1. At the post-transcriptional level, rs139004885 was predicted to disrupt miRNA binding, while 3′UTR rs4986938 showed strong regulatory potential and comparatively high population frequency; by contrast, most other identified SNPs were rare. Clinically, pan-cancer survival analyses indicated worse overall survival (OS) in BRCA for ESR2-Altered cases (HR ≈ 2.25; q < 0.001), but better OS in UCEC (HR ≈ 0.24; q ≈ 0.014) and OV (HR ≈ 0.29; q < 0.001), highlighting a tumor-type-specific association. Conclusions: This integrative analysis prioritizes high-impact ESR2 variants that likely impair ERβ1 structure and shows context-dependent clinical effects. Despite their generally low frequency (except for rs4986938), prospective validation linking variant class to ERβ expression and survival outcomes is needed to support biomarker development and therapeutic applications. Full article

Cutaneous metastases (CMs) represent an uncommon but clinically significant manifestation of advanced malignancies, originating from both solid and non-solid cancers. This review explores the clinical characteristics and prognostic implications of CMs. For solid cancers, CMs are most frequently associated with primary malignancies of the breast, lung, and gastrointestinal tract, presenting as nodules, plaques, or ulcerative lesions. In contrast, CMs from non-solid cancers, such as hematologic malignancies, often exhibit distinct patterns, including diffuse infiltrates or erythematous plaques, mimicking inflammatory dermatoses. Clinical features, as well as dermoscopy, may help, but diagnostic confirmation relies on histopathological evaluation and immunohistochemical studies, which are essential for determining the primary source of the malignancy. Clinically, CMs often signify a poor prognosis, necessitating prompt recognition and tailored management to improve patient outcomes. This comprehensive review aims to enhance clinical understanding and awareness of CMs to facilitate early diagnosis and optimized treatment strategies. Full article

Curcumin (CUR) is a bioactive compound with well-documented therapeutic potential in diverse pathological conditions, encompassing intestinal disorders—most notably colonic cancer—as well as extra-intestinal malignancies such as hepatic, breast, and renal tumors. However, the therapeutic efficacy of CUR is severely constrained by its poor aqueous solubility, chemical instability, and consequent low systemic bioavailability. Nano-scaled carriers (nanocurcumin) enhance CUR solubility and membrane permeability through their reduced dimensions and/or specific interactions with membrane constituents. Nevertheless, conventional nanocurcumin formulations, such as unmodified liposomes, nanocapsules, nanogels, and nanofibers, continue to accumulate substantially in non-target tissues because of their lack of disease-specific tropism. This review focuses on the most recent advances in active targeting strategies for nanocurcumin, specifically receptor-mediated cellular targeting for extra-intestinal pathologies and colon-specific ligand-directed delivery for intestinal disorders. Current methodologies for validating the efficacy of engineered nanocurcumin formulations are critically reviewed, and the prevailing limitations alongside prospective future applications of nanocurcumin are delineated and discussed. Full article