Copper and iron trigger distinct cuproptosis and ferroptosis as homeostasis is disrupted which would drive hepatocellular carcinoma (HCC) progression. Mitochondrial copper overload impairs protein lipoylation and iron-sulfur cluster stability which induces proteotoxic stress through accumulation of lipoylated TCA cycle enzymes. Elevated copper metabolism paradoxically increases their susceptibility to cuproptosis in HCC cells. Ferroptosis is characterized by iron-dependent lipid peroxidation resulting from insufficient antioxidant protection, particularly impairment of the GSH-GPX4 system that normally reduces lipid hydroperoxides. NRF2 and FSP1 serve as key regulators of HCC sensitivity by modulating antioxidant capacity and lipid metabolism. Dual targeting of these pathways offers a promising therapeutic strategy against HCC. Yet direct clinical evidence demonstrating therapeutic benefit from pharmacological induction of cuproptosis or coordinated cuproptosis-ferroptosis targeting in HCC is currently lacking. We explore the differential impacts of cuproptosis and ferroptosis on tumor progression and discuss the potential therapeutic implications of co-regulating these two cell death mechanisms in HCC.

Lenvatinib is a first-line treatment for hepatocellular carcinoma (HCC), though drug resistance may develop with long-term use. to investigate the potential of pachymic acid to enhance lenvatinib's anti-tumor efficacy. HepG2 and LM3 cells were exposed to pachymic acid and/or lenvatinib. Cell proliferation was evaluated using colony formation assays and flow cytometry analysis of apoptosis. Cell invasion was evaluated using wound healing assays and transwell assays. Glucose consumption, lactate production and glycolysis-related protein expression were measured to evaluate aerobic glycolysis status. Tumor-bearing experiments in nude mice were conducted to verify pachymic acid's influence on HCC. Twenty µmol/L pachymic acid substantially inhibited the apoptosis rate (8.5% versus 15.2%, p < 0.001), wound healing rate (59.3% versus 31.0%, p < 0.001), glucose consumption (5.3 µmol/L versus 3.4 µmol/L, p < 0.001) and lactate production (0.7 µmol/L versus 0.3 µmol/L, p < 0.001) in HepG2 cells. Similar results were observed in LM3 cells. Peroxisome proliferator-activated receptor gamma (PPARγ) could be its molecular target that intervenes in aerobic glycolysis of HCC. Notably, pachymic acid exhibited synergistic antitumor efficacy with lenvatinib in both in vitro (cell survival rate: 53.3% in the lenvatinib group versus 33.3% in the pachymic acid + lenvatinib group, p < 0.001) and in vivo models (tumor volume: 483.0 mm³ in the lenvatinib group versus 357.5 mm³ in the pachymic acid + lenvatinib group, p < 0.01). These findings provide a novel perspective, showing that pachymic acid suppresses aerobic glycolysis in HCC by targeting PPARγ. Furthermore, combining pachymic acid and lenvatinib was discovered to produce a synergistic antitumor effect.

Gastric cancer (GC) remains a major malignancy of the digestive system, with a high burden in developing countries where early diagnosis is often limited. As a result, many patients are diagnosed at advanced stages, and despite comprehensive treatment strategies, recurrence rates remain high. These challenges underscore the urgent need for improved diagnostic and therapeutic approaches. Extracellular vesicles (EVs) have attracted increasing attention due to their critical roles in tumor progression and intercellular communication. Emerging evidence suggests that EVs are involved in key processes such as immune modulation, metastasis, and therapeutic resistance, highlighting their potential as biomarkers and therapeutic targets. In this review, we systematically summarize the biological functions of EVs in GC and critically evaluate their translational potential in diagnosis and therapy. We also discuss current challenges, including technical limitations, lack of standardization, and insufficient clinical validation, and propose future directions for advancing EV-based precision medicine.

Metabolic reprogramming characterized by enhanced glycolysis and lactate production plays a critical role in tumor progression and immune regulation. However, the cellular distribution and spatial organization of lactate-glycolysis activity within the lung adenocarcinoma (LUAD) microenvironment remain incompletely understood. We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic datasets from TCGA and GEO cohorts to characterize lactate-glycolysis-associated metabolic heterogeneity in LUAD. AUCell-based scoring was used to quantify metabolic activity at single-cell resolution. Associations with immune infiltration and clinical outcomes were evaluated, and key findings were validated using spatial transcriptomics, quantitative PCR, and immunohistochemistry. Cells exhibiting high lactate-glycolysis activity were predominantly enriched in fibroblasts and neutrophils, indicating that this metabolic program extends beyond malignant cells. A metabolism-associated gene signature, comprising RPS2, GAPDH, and LDHA, was consistently correlated with immune remodeling and an unfavorable prognosis. Spatial transcriptomics further revealed the co-localization of GAPDH and LDHA with neutrophil-enriched regions. These findings were supported by experimental validation in clinical specimens. Our study reveals that lactate-glycolysis reprogramming in LUAD is spatially structured and closely associated with neutrophil-enriched immune remodeling. This metabolism-associated immune regulatory pattern provides insight into the organization of the tumor microenvironment and may have implications for metabolic- and immune-oriented therapeutic strategies in lung adenocarcinoma.

Robotic breast surgery encompasses oncologic resection and cancer-related reconstruction, but the development and structure of this literature remain incompletely characterized. This study mapped publication growth, citation relationships, thematic evolution, and collaboration patterns in the field. Web of Science Core Collection, Scopus, and PubMed were searched through 1 August 2026. After merging, deduplication, and metadata assessment, two reviewers independently screened 769 records; 210 publications from 2012 to 2026 were included. Bibliometric performance indicators, citation and co-citation analysis, bibliographic coupling, keyword mapping, thematic evolution, and collaboration networks were examined. The corpus comprised 755 authors and 81 sources, with an annual growth rate of 24.5%; 132 publications (62.9%) appeared between 2023 and the search cut-off. Journal of Robotic Surgery was the most productive source. China and South Korea led corresponding-author output, whereas the United States occupied the principal bridging position in the country collaboration network. Nipple-sparing mastectomy and breast reconstruction dominated the conceptual structure. Citation and thematic analyses indicated a progression from technical feasibility toward learning curves, comparative outcomes, perioperative complications, and oncologic assessment, with single-port procedures and robot-assisted autologous reconstruction emerging as recent research directions. The international co-authorship rate was 13.33%, and collaboration remained concentrated within a limited number of research communities. These patterns describe research activity rather than clinical effectiveness. Further multicenter studies using standardized outcomes and longer oncologic follow-up are needed to evaluate the comparative clinical value of evolving robotic approaches.

Immunotherapy through adoptive cell therapy (ACT) has become an effective cancer treatment method, using genetically modified immune cells or immune cells grown outside the body. The ACT methods use chimeric antigen receptor T (CAR-T) cells, with proven results for blood cancers, while tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR)-engineered T cells serve as effective methods to fight against solid tumors and intracellular antigens. The current medical field uses natural killer (NK) cell-based therapies because of their natural ability to destroy cells, their lower incidence of graft-versus-host disease, and their capability to generate readily available therapeutic products through allogeneic medical procedures. The clinical utilization of ACTs has been facing multiple obstacles, stemming from antigen diversity, immune system resistance, treatment-related adverse effects, and difficulties in production. The researchers are advancing multiple solutions to resolve current challenges through developing multi-targeted receptor designs and gene-editing technologies, enhanced cell persistence strategies, and scalable manufacturing platforms. The next-generation ACT platforms will achieve improved therapeutic results through a mix of combination therapies, biomarker-driven patient selection, and advanced manufacturing technologies. Emerging areas of biological research demonstrate how adoptive cell therapies can develop into key components of precision cancer immunotherapy. In this review, we discussed the principles, benefits, and challenges of ACT, with a focus on potential solutions to overcome these obstacles.

Resistance to platinum-based chemotherapy in epithelial ovarian cancer is frequently driven by dysregulation of apoptotic pathways and overexpression of inhibitor of apoptosis proteins (IAPs). Smac mimetics, such as Birinapant, target IAPs and modulate TNF-α-associated signaling; however, their therapeutic efficacy is highly context-dependent.

We investigated the effects of Birinapant in combination with Cisplatin in ovarian cancer cell lines with distinct sensitivity profiles (SKOV3 and MDAH-2774), along with normal human endometrial stromal cells (HESC) to assess selectivity. Cell viability was measured using the MTT assay, and drug interactions were evaluated using the Chou-Talalay method. Apoptosis was quantified by Annexin V/PI flow cytometry. Protein expression (cIAP1, NF-κB, Caspase-3/8) was analyzed by immunofluorescence, and gene expression (BIRC2, CASP3/8, RELA, TNF) was assessed by RT-qPCR.

The Birinapant-Cisplatin combination significantly reduced cell viability in SKOV3 cells and demonstrated strong synergistic effects (CI = 0.057-0.237), accompanied by substantial dose reduction. In contrast, MDAH-2774 cells exhibited limited responsiveness and predominantly antagonistic interactions. Mechanistically, combination treatment in SKOV3 cells was associated with reduced cIAP1 expression, suppression of NF-κB signaling, and activation of Caspase-8 and Caspase-3. Notably, TNF Mrna expression was strongly increased (log₂FC ≈ + 5.6), supporting involvement of TNF-associated apoptotic signaling.

Birinapant increased the sensitivity of SKOV3 ovarian cancer cells to cisplatin by enhancing TNF-α-associated apoptotic signaling, while this synergistic effect was not observed in MDAH-2774 cells, emphasizing the importance of cellular context in determining SMAC mimetic responses. Our findings suggest that TNF-α responsiveness, cIAP1 (BIRC2)-related signaling, and the ability of cancer cells to activate apoptotic pathways, particularly caspase-8, may serve as potential biomarkers for identifying tumors more likely to respond to Birinapant-based combination therapies. Further studies using additional ovarian cancer models and clinical samples are required to validate the predictive value of these biomarkers.

A major change has taken place in the treatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer in recent decades, largely as a result of the development of targeted anti-HER2 treatment. This type of breast cancer accounts for approximately 13 % of all breast cancer cases diagnosed annually. Treatment options have evolved from a single HER2-targeted monoclonal antibody (trastuzumab) to a range of targeted and potent drugs. Collectively, these advances have led to significant improvements in prognosis and survival for patients with HER2-positive breast cancer. This clinical review outlines the development of HER2-targeted therapies and key principles of current treatment for both localised and metastatic disease.

Effective lung-targeted therapies can directly treat pulmonary diseases and engage tissue-resident immunity for lasting effects. However, protein delivery systems specifically targeting the lung remain scarce. Here, we report the discovery of phenylborate (PBA)-functionalized polymeric nanocapsules that enable efficient pulmonary delivery of protein cargos following systemic administration. Systematic structure-activity relationship studies revealed that PBA incorporation strongly correlates with enhanced lung tropism, establishing a previously unrecognized materials design principle for lung-targeted protein delivery. Leveraging this capability, we demonstrate that lung-targeted antigen delivery induces robust tissue-resident memory T cell responses within the pulmonary microenvironment and suppresses tumor growth in preclinical models of lung metastasis. Together, these findings redefine the in vivo functional role of phenylborate in nanocarrier systems and establish a versatile materials platform for lung-targeted protein therapeutics and site-specific immune modulation.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality, with limited curative options. Histotripsy is a noninvasive focused ultrasound ablation technique that destroys tumors through acoustic cavitation rather than heat-based methods, offering an alternative to radiofrequency and microwave ablation. This review traces histotripsy from preclinical development to U.S. Food and Drug Administration (FDA) approval for liver tumors. Unlike thermal methods, histotripsy creates precise mechanical tissue fractionation while preserving critical structures, including blood vessels and bile ducts. The technology uses short, high-pressure ultrasound pulses to generate cavitation bubble clouds that liquefy targeted tissue without thermal damage. Preclinical studies demonstrated complete tumor ablation with robust immune cell infiltration, suggesting potential abscopal effects. Clinical trials, including THERESA and #HOPE4LIVER, confirmed safety, with #HOPE4LIVER demonstrating short-term efficacy, achieving approximately 95% technical success and approximately 90% 1-year local control rates. Histotripsy received FDA approval in October 2023 for treating liver cancer. The technology shows promise for perivascular lesions where heat-sink effects compromise thermal ablation. Current evidence supports optimal outcomes for tumors 3 cm or smaller, with ongoing research exploring combinations with immunotherapy and applications beyond HCC. Histotripsy represents a paradigm shift in local ablation, offering mechanical precision combined with potential systemic immunostimulatory benefits. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.