Hepatocellular carcinoma (HCC) continues to impose a substantial global health burden, with the incidence and the mortality remaining closely aligned despite major advances in diagnostics and therapeutics. Over the past three decades, screening and treatment technologies have evolved from single-marker surveillance to risk-stratified, multimodal assessment, and from standalone local therapies to integrated radiologic and immunologic strategies. However, these innovations have not translated into proportional population-level benefits, as early detection rates remain persistently low across many regions. This review provides a comprehensive synthesis of the three-decade evolution in HCC surveillance and treatment, highlighting how biomarker innovation, imaging standardization, and emerging systemic therapies have reshaped clinical practice, while identifying key barriers that continue to limit real-world impact, including metabolic disease-related imaging challenges, inconsistent long-term surveillance adherence, and pronounced disparities in healthcare access. By integrating epidemiologic trends, clinical evidence, and technological advances, this review emphasizes a central principle: meaningful improvement in HCC outcomes depends less on the availability of sophisticated tools than on the timely identification and management of patients within the curative window. The insights presented aim to develop future precision-based, equitable, and multimodal strategies for HCC prevention and control.

Estrogen receptor alpha (ERα) defines the biology of estrogen receptor-positive breast cancer by regulating both tumor-intrinsic signaling and the surrounding immune microenvironment. Beyond its genomic and non-genomic actions, ERα modulates cytokine production, antigen presentation, and the activity of innate and adaptive immune cells, contributing to a low mutational burden, weak immunogenicity, and an immune-excluded tumor state. Through interactions with NF-κB, suppression of interferon pathways, and regulation of myeloid and lymphoid cell functions, ERα promotes immune tolerance and supports tumor progression. These immunoregulatory effects help explain limited responses to endocrine therapy and the poor performance of immune checkpoint inhibitors in ER-positive diseases. Emerging strategies, including next-generation selective estrogen receptor degraders and combinations with CDK4/6 inhibitors or immunotherapy, aim to overcome ERα-driven immune suppression. Understanding ERα-mediated immune regulation will be essential for developing more effective therapeutic approaches for ER-positive breast cancer.

Cancer survivors may exhibit biological and metabolic changes linked to both cancer and its treatment. This systematic review aimed to compare metabolic and biological aging-related biomarkers between cancer survivors and healthy individuals. The primary electronic databases utilized to search papers from 2019 to 2024 were PubMed, Scopus, and Web of Science. Boolean operators were combined with specific keywords and MESH terms in searching the articles. After excluding protocol papers, studies with incorrect designs or populations, and animal studies, 27 articles were selected for data extraction, synthesis, and quality evaluation. The articles were checked for quality by using the National Institutes of Health (NIH) checklist for observational cohort and cross-sectional studies. Cancer survivors had significant differences in aging-related metabolic and biological biomarkers compared to a healthy population. These include aberrant DNA methylation (hypermethylation, hypomethylation, and epigenetic modification), abnormal expression levels of lipid profiles (high-density lipoprotein, low-density lipoprotein level, malondialdehyde, and apolipoprotein C-1), inflammatory markers (interleukins, C-reactive protein, and TNF-α), immune-senescence (Cellular Communication Network Factor 3 protein), energy regulation (leptin, adiponectin, and mitochondria function profiles), and poor oral and bone health. These findings reflect the accelerated biological age and increased vulnerability to age-related diseases among cancer survivors, as compared to healthy populations. However, considering the cross-sectional design limitations, causal relationships between cancer diagnosis and alterations in biological aging cannot be confirmed. To establish whether cancer itself contributes to accelerated aging, future longitudinal studies are needed that assess metabolic and biological biomarkers in individuals from the time of diagnosis onward.

Hepatocellular carcinoma (HCC) is a highly malignant liver cancer that metastasizes to various organs. Esculetin, a natural dihydroxy coumarin derivative, has been shown to have a variety of pharmacological properties, including immune-enhancing, antioxidant, and anti-inflammatory effects. Esculetin is also known to have potent anticancer activity; however, studies on its ability to inhibit cancer cell metastasis are relatively rare. In this study, we investigated how esculetin inhibits the migration and invasion of human hepatocellular carcinoma cell lines Hep3B and HepG2, and elucidated the underlying mechanisms. Our results showed that esculetin markedly suppressed the migration and invasion of HCC cells, and this was associated with a decrease in the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and increased expression levels of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. In addition, esculetin enhanced the tightening of tight junctions by suppressing the expression of claudin family proteins.

Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.

Oral cancer is a major global health concern, with high incidence and mortality rates, especially in high-risk populations. Early diagnosis remains a challenge, and current treatments, such as surgery, radiation, and chemotherapy, have limited effectiveness, particularly in advanced stages. Recent advances in targeted therapies and immunotherapy offer promising alternatives, providing more precise and personalized treatment options. Targeted therapies, such as epidermal growth factor receptor inhibitors, aim to disrupt specific molecular pathways in tumor growth, while immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy, enhance the body's immune response to fight cancer. Combination therapies, integrating both targeted and immune strategies, are being explored to overcome the limitations of single-agent treatments. This review highlights the current strategies in the prevention and treatment of oral cancer, discusses emerging therapies, explores future research directions, focusing on optimizing existing treatments, identifying new biomarkers, and developing innovative therapeutic approaches. The potential of personalized medicine and combination therapies offers new hope for improving survival rates and quality of life for oral cancer patients.

Hepatocellular carcinoma (HCC) is the most common and lethal type of primary liver cancer, frequently arising from chronic liver injury and inflammation. Despite treatment advancements, HCC prognosis remains poor, emphasizing the need for effective preventive and therapeutic strategies. This study investigates the hepatoprotective and anti-tumor effects of Hongjam, a steamed freeze-dried silkworm powder, in a diethylnitrosamine (DEN) and thioacetamide (TAA)-induced HCC mouse model. Mice were administered DEN intraperitoneally for 8 weeks, followed by TAA in drinking water for 9 weeks, with Hongjam supplementation (0.01, 0.1, and 1 g/kg) provided daily through food. Hongjam markedly reduced the tumor incidence, the size, and the histological lesions compared to the DEN/TAA group. Serum biochemical analysis revealed reduction in liver damage markers, including alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin, with a notable decrease in total bilirubin surpassing. Immunohistochemical and Western blot analyses demonstrated that Hongjam downregulated expression of proliferation markers, including Ki67, phosphorylation of protein kinase B, and proliferating cell nuclear antigen, while upregulating the pro-apoptotic protein Bcl-2-associated X protein, indicating its dual role in suppressing proliferation and promoting apoptosis. Furthermore, Hongjam inhibited angiogenesis by suppressing the expression of key markers, including interleukin 6, VEGF, hypoxia-inducible factor-1 subunit alpha, platelet-derived growth factor subunit beta, matrix metalloproteinase-2, and cluster of differentiation 31, thereby disrupting the tumor microenvironment. These findings suggest that Hongjam exerts multifaceted protective effects against HCC by targeting proliferation, apoptosis, and angiogenesis pathways, while also mitigating liver damage. This study highlights the potential of Hongjam as a functional food or a complementary therapeutic agent for HCC prevention and management.

Shiga toxin-producing Escherichia coli is the most prevalent bacterial strain responsible for Shiga toxin-related infections. While Shiga toxin is inherently toxic, it has potential therapeutic applications as a component of anticancer drugs. Despite its association with infections and harmful effects on human health, Shiga toxin is being explored as a viable element in drug delivery systems targeting cancer cells. The findings indicate that the production of mutated bacteria containing Shiga toxin is an effective preventive strategy for immunization against these toxins. Furthermore, the B subunit of Shiga toxin shows promise for imaging cancer cells, opening new paths for therapeutic interventions.

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Liver cancer is prevalent worldwide and associated with a high mortality rate. Therefore, developing novel drugs derived from natural products to reduce the side effects of chemotherapy is urgently needed. In this study, the inhibitory effect of Dendropanax morbifera Leveille extract (DME) on growth of hepatocellular carcinoma (HCC) cells and its underlying mechanisms were investigated. DME suppressed the growth, migration, and invasion of SK-Hep1 human HCC cells. It also reduced the expression of the G0/G1 phase regulator proteins cyclin-dependent kinase (CDK) 4, cyclin D, CDK2, and cyclin E, thereby inducing G0/G1 arrest. Moreover, DME treatment reduced the expression of antiapoptotic proteins, including caspase-9, caspase-3, PARP, and Bcl-2 and increased the expression of the proapoptotic protein, Bax. DME also increased reactive oxygen species production and reduced the cellular uptake of rhodamine 123. DME treatment increased the levels of p-p38 and p-FOXO3a in a dose-dependent manner and decreased those of p-PI3K, p-AKT, p-mTOR, and p-p70 in SK-Hep1 cells. In addition, combined treatment with DME and LY294002, an AKT inhibitor, significantly reduced p-AKT levels. In summary, these results show that the PI3K/AKT/mTOR signaling pathway is involved in DME-mediated inhibition of proliferation, migration, and invasiveness, and induction of apoptosis of HCC cells.