Milad Ashrafizadeh

Breast cancer is one of the leading causes of death worldwide. The aggressive behaviour of breast tumor results from their metastasis. Notably, the brain tissue is one of the common regions of metastasis, thereby reducing the overall survival of patients. Moreover, the metastatic tumors demonstrate poor response or resistance to therapies. In addition, breast cancer brain metastasis provides the poor prognosis of patients. Therefore, it is of importance to understand the mechanisms in breast cancer brain metastasis. Both cell lines and animal models have been developed for the evaluation of breast cancer brain metastasis. Moreover, different tumor microenvironment components and other factors such as lymphocytes and astrocytes can affect brain metastasis. The breast cancer cells can disrupt the blood-brain barrier (BBB) during their metastasis into brain, developing blood-tumor barrier to enhance carcinogenesis. The breast cancer brain metastasis can be increased by the dysregulation of chemokines, STAT3, Wnt, Notch and PI3K/Akt. On the other hand, the effective therapeutics have been developed for the brain metastasis such as introduction of nanoparticles. Moreover, the disruption of BBB by ultrasound can increase the entrance of bioactive compounds to the brain tissue. In order to improve specificity and selectivity, the nanoparticles for the delivery of therapeutics and crossing over BBB have been developed to suppress breast cancer brain metastasis.

CRC is regarded as a worldwide health issue, exhibiting considerable geographic differences. The current research examines the global epidemiology of CRC (1990–2021) and forecasts trends until 2050, focusing specifically on Australasia. We performed an extensive analysis using data from the Global Burden of Disease 2021 study to calculate age-standardized incidence and mortality rates (ASIR/ASMR) for CRC from 1990 to 2021. Analyses were divided by sex, age, geographic area, and SDI. Temporal trends were evaluated by utilizing EAPC. We assessed the impact linked to significant modifiable risk factors such as dietary risks, elevated body mass index, alcohol consumption, smoking, and lack of physical activity using comparative risk evaluation techniques. To forecast CRC mortality until 2050, we utilized a Bayesian Age-Period-Cohort (BAPC) model that includes demographic and temporal factors. Regions with high SDI exhibit the highest incidence of CRC but show decreasing trends, whereas regions with middle SDI are experiencing increasing burdens. Australasia, despite its historically high rates, accomplished notable reductions in mortality (–1.95% per year), positioning itself alongside Austria and Germany as frontrunners in CRC management. The rate of CRC occurrence is believed to be greater in males than in females. Dietary elements are the primary alterable risk factor worldwide, particularly in affluent areas. Forecasts and future estimates indicate additional declines in mortality rates in high-income areas, while transitioning economies face rising burdens. The burden of CRC is moving towards developing areas. Australasia showcases effective cancer management via screening and treatment, offering essential insights for global policies and strategies addressing changeable risks. The occurrence of colorectal cancer is increasing in middle-SDI regions, whereas it is decreasing in high-SDI areas like Australasia. Australasia saw a − 1.95% yearly decline in mortality rates due to successful screening and treatment efforts. High BMI and dietary risks are the primary modifiable factors contributing to colorectal cancer deaths worldwide. Throughout various regions, males consistently exhibit greater incidence and mortality rates for colorectal cancer. Worldwide forecasts suggest persistent decreases in mortality rates in high-income areas, while other regions face increasing burdens by 2050.

Gastrointestinal(GI) cancers rank among the most common and lethal tumors. Traditional therapies face limitations in the early diagnosis, accurate targeting, and treatment effectiveness. Metallic nanoparticles (MNPs) such as Au, Ag, and iron oxide present various promising opportunities owing to their exceptional physicochemical properties including high surface area-to-volume ratios, tunable surface chemistry, and biological interactions. This review assesses the capabilities of MNPs in GI cancers, concentrating on the drug delivery, imaging, photothermal therapy (PTT), and the enhancement of radiotherapy. The primary findings encompass using gold nanoparticles (AuNPs) for the targeted drug delivery, photothermal-induced tumor ablation, and radiosensitization in colorectal, pancreatic, and gastric cancers. AgNPs can not only enhance chemotherapy and photodynamic therapy (PDT) but also induce apoptosis. Iron oxide nanoparticles (IONPs) aid in magnetic drug targeting, enhance magnetic resonance imaging (MRI) contrast, and enable combined chemo-photothermal therapy. Metal-organic frameworks (MOFs) facilitate drug delivery, multimodal imaging, and combination treatments, including photodynamic and immunotherapy, for colorectal and pancreatic cancers. The review emphasizes the recent advancements in MNP-based theranostic platforms, showcasing their ability to enhance the early detection, overcome drug resistance, and boost the therapeutic index. The obstacles such as off-target effects, scalability and chronic toxicity are addressed, along with methods for enhancing MNP design and its clinical use. This review emphasizes the transformative possibilities of MNPs in tackling the worldwide challenge of GI cancers. • Metallic nanoparticles facilitate precise drug delivery to gastrointestinal cancer, increasing effectiveness while minimizing side effects. • Metalic nanoparticles and MOFs enhance diagnostic imaging for the early detection of cancer and monitoring treatment. • Gold and silver nanoparticles improve the efficacy of photothermal ablation and radiotherapy. • Metallic nanoparticle platforms merge treatments to address drug resistance in gastrointestinal cancers. • Metallic nanoparticles and MOFs enable tailored theranostic approaches in precision medicine.

Epithelial-mesenchymal transition (EMT) is a reversible process that enables carcinoma cells to become invasive and therapy-resistant, thereby affecting clinical outcomes such as relapse and treatment failure. In tumors, EMT is triggered by pathways such as TGF-β, Wnt/β-catenin, Notch, PI3K/Akt/mTOR, MAPK, hypoxia, and inflammatory cytokines. These activate EMT-inducing transcription factors, including Snail, Slug, Twist, and ZEB1/2. Noncoding RNAs, like the ZEB–miR-200 axis, also play roles. These changes create intermediate epithelial–mesenchymal states linked to collective migration, stemness, tumor recurrence, and therapy resistance. EMT also promotes immune evasion. Myeloid and stromal cells, especially tumor-associated macrophages and MDSCs, promote EMT and suppress antitumor immunity. EMT reduces antigen presentation, increases immune checkpoints such as PD-L1, and alters chemokines to attract immunosuppressive T cells, helping tumors evade detection. EMT contributes to multidrug resistance by altering cell adhesion and motility and by activating kinases such as STAT3, AXL, and EGFR/ERK. Targeting or reversing EMT can increase tumor sensitivity to treatment and improve outcomes. Combinations of EMT inhibitors (e.g., TGF-β and PI3K inhibitors), epigenetic therapies, and RNA-based reprogramming are being evaluated. New multi-omics and liquid biopsy technologies enable real-time monitoring of EMT status to support more personalized care. Recognizing EMT as a key driver of tumor progression creates new opportunities for targeted treatment.