Triple-negative breast cancer (TNBC) poses a major challenge in women's health due to its aggressive nature and lack of targeted therapies. β-Elemene, a sesquiterpene derived from Curcuma wenyujin, has shown clinical benefits in TNBC, but its mechanisms of action, particularly regarding the immune and metabolic tumor microenvironment, are still poorly defined. In this study, we employed single-cell RNA sequencing and untargeted metabolomics to investigate how β-elemene reshapes the cellular and metabolic landscape of TNBC in a 4T1 orthotopic mouse model. Our results revealed that β-elemene inhibited both primary tumor development and pulmonary metastasis in TNBC. Single-cell analysis identified 11 distinct cell subpopulations, with cancer-associated fibroblasts (CAFs) showing the most pronounced reduction upon β-elemene treatment. Further mechanistic studies indicated that β-elemene enhanced antigen presentation in tumor cells while suppressing CAF-mediated extracellular matrix remodeling and focal adhesion, thereby disrupting their pro-tumorigenic cellular communication. Additionally, metabolomic profiling revealed a significant downregulation of prostaglandins, including PGH2, PGF2α, PGD2, and PGE2 in the arachidonic acid metabolism pathway, which was critically implicated in immune regulation. The above findings would provide the first comprehensive elucidation of β-elemene's dual immunomodulatory and metabolic effects in TNBC, underscoring the potential of natural compounds to augment antitumor immunity.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men worldwide. Understanding the signaling pathways and molecular mechanisms that drive PCa development and progression is essential for developing new treatments. In this review, we provide an overview of the history and advancements in PCa's detection, diagnosis, surgical intervention, hormonal therapy, chemotherapy, and radiotherapy. We reviewed genetic alterations and their roles in PCa tumorigenesis. We also summarized the molecular mechanisms that drive the transition from castration-sensitive PCa (CSPC) to castration-resistant PCa (CRPC), along with factors that promote lineage plasticity from AR-positive CRPC to neuroendocrine PCa (NEPC) and double-negative PCa (DNPC). We further examined recent advances in immunotherapies, including CAR-T, PARP inhibitors, proteolysis-targeting chimeras (PROTACs), and antibody-drug conjugates (ADCs). Finally, we provide perspectives regarding the opportunities and challenges in detection, diagnosis, and therapy of PCa and future directions for the investigation of molecular mechanisms of prostate cancer development, progression, and therapy resistance. This review provides a framework that connects historical milestones with current molecular insights and offers a roadmap for future precision oncology strategies in prostate cancer.

Ferroptosis is a redox-governed, non-apoptotic cell death program driven by iron-dependent lipid peroxidation. Its execution depends on the balance between reactive oxygen species (ROS) generation and hierarchical antioxidant defenses. Despite extensive biochemical mapping, an integrated framework delineating how diverse redox defense systems converge to dictate ferroptotic sensitivity across tumor contexts remains lacking. This review delineates the hallmarks and molecular mechanisms of ferroptosis, examining how ROS sources within mitochondrial, the endoplasmic reticulum, membranes, and the cytoplasm drive lipid peroxidation. The antioxidant landscape is systematically classified into three functional tiers: (1) the primary canonical glutathione-GPX4 axis, (2) secondary non-canonical and radical-trapping systems including FSP1-CoQ10, GCH1-BH4, peroxiredoxins, and vitamin K, and (3) tertiary metabolic support and detoxification systems encompassing thioredoxin, AKR1C enzymes, SOD-catalase, and NADPH regeneration. The regulation of these defenses by master signaling hubs including NRF2, AMPK-mTOR, ATF4, STAT3, Wnt/beta-catenin, p53, and ncRNAs is evaluated, alongside oncogenic metabolic adaptations creating exploitable vulnerabilities in high-plasticity states including epithelial to mesenchymal transition, cancer stem cells, hypoxic, matrix-detached, and chemoresistant cells. Tumor microenvironment crosstalk among cancer-associated fibroblasts and immune effectors, including CD8⁺ T cells, natural killer cells, macrophages, and myeloid-derived suppressor cells, and therapeutic strategies spanning pharmacological and nanomaterial-based approaches are further examined. Collectively, this synthesis furnishes a mechanistic framework for precision exploitation of ferroptosis across oncological contexts.

Glioma is one of the most invasive tumors in the central nervous system. Traditional treatment is limited by the blood-brain barrier and tumor drug resistance, and the prognosis of patients is very poor. At present, there is a lack of a comprehensive review that can systematically integrate various nanotechnology strategies to meet these challenges. This review first analyzes the brain biological barrier and glioma microenvironment that nanoparticles delivery must overcome. Furthermore, the key strategies for crossing these barriers, such as receptor-mediated transport and physical assistance methods, are systematically reviewed. This paper focuses on the design and characteristics of various nano-platforms (including inorganic, organic and biological nanoparticles), and discusses in detail how they can drive multimodal synergistic therapies such as chemotherapy, radiotherapy and immunotherapy to improve the curative effect and overcome drug resistance. The purpose of this paper is to provide an integrated perspective for researchers in the field to overcome the delivery barrier and realize innovative therapy by nanotechnology, and to provide a theoretical framework and design ideas for promoting the clinical transformation of the next generation of intelligent and personalized nano-drugs for glioma.

Evidence is limited on long-term prognosis, and little is known about the immunotranscriptome in esophageal squamous cell carcinoma (ESCC) patients with different tumor regression grades (TRGs) after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Herein, the prognostic analysis of 300 ESCC patients treated with NCRT and surgery revealed that the TRG0/1 group (good responders) had significantly longer disease-free survival (DFS) and overall survival (OS) than the TRG2/3 group. Integrating TRG and pathological N-stage, we developed a tumor regression grade and lymph node (TRGN) staging system, which demonstrated superior prognostic stratification and distinct recurrence patterns. Transcriptome analysis showed that compared to the TRG2/3 group, the TRG0/1 group exhibited higher scores in immune checkpoint blockade (ICB) response-related signatures, greater similarity to ICB responder samples, and increased T-cell receptor clonality, suggesting enhanced immunotherapy sensitivity. Integrating scRNA-seq and RNA-seq, we identified B cell, CD8+ T cell, and NK cell subsets associated with better NCRT responses, within which a tight cell communication network potentially mediating antitumor immunity was formed. Multiplexed immunohistochemistry confirmed that the spatial relationship between CD8+ T/NK cells and tumor cells improved the NCRT response. These findings confirmed the prognostic value of TRGs and can help guide surveillance and treatment strategies in ESCC.

Oxysterols are bioactive cholesterol oxidation products that link lipid metabolism, inflammation, immune regulation, and tumor progression. This review summarizes the generation, sensing, and cancer-related functions of major oxysterols, with a particular emphasis on 25-hydroxycholesterol and 27-hydroxycholesterol. It begins by outlining both enzymatic and non-enzymatic pathways for oxysterol production, as well as the key receptors and signaling pathways involved, including LXR, SREBP, ER, GPER, EBI2/GPR183, NF-κB, and PI3K/AKT/mTOR. The review then compares the ways in which oxysterols regulate tumor cell proliferation, invasion, metastasis, stromal remodeling, immune suppression, and therapeutic resistance across various malignancies, revealing a context-dependent duality of pro-tumorigenic and tumor-suppressive effects. Importantly, this review systematically evaluates pharmacological strategies that target oxysterol-producing enzymes, sensing receptors, and downstream signaling nodes. Emerging advances are highlighted, including the first in vivo validation of selective CYP27A1 blockade using Dafadine-A, Phase I clinical evaluations of LXR agonists demonstrating T cell expansion, GPR183-engineered CAR-T cells that exploit oxysterol gradients for enhanced tumor infiltration, and three preclinical combination frameworks that pair oxysterol pathway modulation with immune checkpoint blockade, targeted therapies, or metabolic multi-node strategies. By integrating mechanistic, preclinical, and clinically relevant evidence, this review clarifies how oxysterol biology may inform biomarker discovery, patient stratification, and future precision cancer therapy.