Breast cancer (BC) is the most frequently diagnosed malignancy among women worldwide, with a high incidence and mortality rate. Despite advances in treatment, approximately 10%-15% of patients with BC still face recurrence. Therefore, improving BC therapy remains a significant challenge. In this article, we provide a detailed overview, categorizing and elaborating the developments of current research progress on nanodrug delivery systems based on ferroptosis for BC treatment. By increasing the iron content in BC cells and inhibiting the defense system against ferroptosis, the accumulation of lipid peroxides is promoted, and ferroptosis is induced in BC cells. In addition to directly targeting tumor cells, nanodrug delivery systems can remodel the tumor microenvironment, inhibit BC primary growth, and prevent distant metastasis. These nanomaterials, after drug loading and modification, possess characteristics such as smart activation, controlled release, specific targeting, good biocompatibility, and long circulation time, thereby enhancing the efficacy of BC treatment. We also classify and discuss the mechanisms and advantages of different types of nanomaterials. Finally, we discuss how multifunctional nanosystems can sensitize ferroptosis when combined with radiotherapy, chemotherapy, immunotherapy, and phototherapy to achieve synergistic effects in BC treatment. This work reveals the potential of ferroptosis-based nanomaterials in overcoming BC, analyzes the limitations of the clinical application and proposes possible solutions, offering a promising direction for future treatment strategies.

In the development of human cancers, alterations in the process of cell mitosis frequently play a role. In recent years, an increasing number of researchers have focused on the phenomenon of cancer resulting from kinetochore-microtubule attachment imbalance.Spindle pole body component 25 (SPC25) is essential for the organization of the spindle devices and chromosome separation. SPC25 has a significant role in the occurrence and development of malignant tumors, but its role in lung adenocarcinoma has not been established. This study utilizes the TCGA database and centrosome assembly checkpoint specialized resources to explore the molecular mechanisms of lung adenocarcinoma and its interaction with the immune system. By using the "limma" and "survival" R software packages and Venn diagram analysis, we identify differentially expressed mRNAs that are associated with lung adenocarcinoma prognosis and play a role in centrosome assembly checkpoint regulation, and determine SPC25 as the target gene. We use the "pROC" software package to draw ROC curves to evaluate its diagnostic potential, perform chi-square tests and logistic regression models to analyze its relationship with clinical pathological features. Cox regression analysis deepens our understanding of its prognostic evaluation role, and enrichment analysis reveals its biological functions and signaling pathways. We also explore the correlation between SPC25 and lung adenocarcinoma immune infiltration by combining ssGSEA and Spearman analysis. The objective of this study was to investigate the association between SPC25 and the prognosis as well as immune infiltration in lung adenocarcinoma, aiming to establish a crucial molecular foundation for early non-invasive diagnosis and immunotherapy of lung adenocarcinoma.

In Chronic Lymphocytic Leukemia (CLL), t(14;19)(q32;q13), leading to the overexpression of BCL3, is found in ∼1% of cases and is associated with an aggressive disease. In this study, leveraging a large CLL patient cohort collected thanks to an international collaboration, we investigate for the first time the circular transcriptome (circRNAome) associated with the rare t(14;19), in comparison with CLL without t(14;19) and B cells of age-matched healthy donors. We described the circRNAs commonly dysregulated in CLL, including circCSNK1G3 and circEXOC6B(3–5), which were depleted, and circZNF609 and circLPAR3, which were overexpressed in malignant cells. Of importance, we disclosed the circRNA signature of CLL with t(14;19), formed by circRNAs with expression significantly altered specifically in link with this lesion, ectopically expressed like circCDK14(3–4), circCORO1C, circCLEC2D, and circEMB, or downregulated like circCEP70(3–6). Several of these molecules were previously shown to be dysregulated or play a role in cancer, whereas most of the signature circRNAs deserve further investigation. CLL patients with high circCORO1C and circCLEC2D expression had significantly worse clinical outcomes, with shorter time to first treatment and overall survival. This study disclosed new molecular features of the aggressive CLL subtype with t(14;19).

The online version contains supplementary material available at 10.1186/s13045-025-01725-y.

Breast cancer (BC) remains a leading cause of cancer-related mortality in women, with complex mechanisms driving its initiation, progression, and resistance to therapy. In recent years, the tumor microenvironment (TME) has gained attention for its critical role in shaping tumor behavior, where small extracellular vesicles (small EVs) have emerged as key mediators of intercellular communication. These vesicles carry a diverse cargo of proteins, lipids, DNA, and various non-coding RNAs-such as miR-21, miR-155, and miR-1246-mirroring the molecular status of their originating cells. This review highlights the roles of small EVs in immune modulation, stromal remodelling, and metastatic niche formation, emphasizing their contribution to therapy resistance and immune evasion. We discuss recent updates on EV biogenesis, characterisation and isolation techniques, such as ultracentrifugation, immunoaffinity and microfluidic systems. We also critically evaluate their potential for clinical application and how well they conform to the MISEV2023 guidelines. Furthermore, we examine small EVs as diagnostic tools in liquid biopsies and compare them with conventional methods such as mammography and tissue biopsies. We also discuss organotropism mediated by small EV cargo (e.g., integrins α6β4, αvβ5) and the diagnostic potential of protein and lipid signatures (e.g., PD-L1, CD63, and exosomal lipidomics). Therapeutically, we explore engineered small EVs for drug delivery, gene modulation, and immune activation, addressing challenges of targeting efficiency, in vivo stability, immunogenicity, and clinical scalability. The review discusses ongoing clinical trials involving small EVs in BC and highlights key translational gaps between preclinical advances and clinical implementation. Finally, we explores how integrating artificial intelligence, single-cell transcriptomics, and multi-omics approaches can help overcome major challenges such as small EV heterogeneity and tracking limitations. Crucially, this integration enables a more tailored understanding of each patient's tumor biology, reducing therapeutic failures by guiding more personalized and effective treatment strategies. Overall, small EVs represent a transformative tool in precision oncology, contingent on resolving key challenges in their clinical translation.

Anatomical variations that occur during radiation therapy in head and neck cancer (HNC) patients can lead to significant dosimetric changes. The purpose of this study is to evaluate dosimetric and volume changes in key anatomical structures for different treatment sites in HNC patients, and to determine the percentage of patients who need adaptive radiotherapy (ART) per treatment site.

A total of 1,740 megavoltage computed tomography (MVCT) images from 58 HNC patients treated with helical tomotherapy (HT) were exported to the PreciseART™ (Accuray) software. Volume changes in the planning target volume (PTV) and the organs at risk (OARs) in the planning stage and the first and last fractions of treatment were calculated. The differences between the values of actual accumulated and initial plan doses were used to determine which patients benefit ART.

The average volume changes between the planning stage and the first fraction were 3.93%, 4.49%, and 6.46% for the PTV, brainstem, and spinal cord, respectively, for all patients. However, the average volume changes between the first and last fractions of treatment were relatively small and included 0.84%, 3.62%, and 1.19% for the PTV, brainstem, and spinal cord, respectively. The average dose changes between the initial planned dose and the actual cumulative dose in the last fraction were in the range of 10.43-30.81%; 4.66-11.61%; 3.73-9.97%; and - 0.17-5.40% for the brainstem, left parotid, right parotid, and spinal cord, respectively, for all patients. A maximum of 10.53%, 28.57%, and 18.18% of patients with oral cavity, larynx, and nasopharyngeal cancers, respectively, needed ART. Patients with salivary gland cancers did not need ART.

Although monitoring the volume and dose changes of the tumor and OARs during the course of radiation therapy is important, not all patients need ART. Criteria such as weight loss and rapid tumor shrinkage should be considered when selecting candidate patients for ART. The time interval between CT simulation and the first fraction also plays an important role in the difference in the volume and dose to organs during the course of radiation therapy.

Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal-organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃]²⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe³⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe³⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered ¹O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe³⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal-ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies.

There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.

Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood.

We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments.

We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control.

The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies.

It is estimated that over 85% of human transcripts are non-coding RNAs, which play an important role in the regulation of numerous biological processes and are closely associated with the development of human cancers. Nevertheless, the functions of the vast majority of non-coding RNAs are yet to be clearly elucidated.

Long non-coding RNA (lncRNA) LINC02320 was screened out by RNA-sequencing using paired CRC samples. The level of LINC02320 in colorectal cancer (CRC) tissues and cell lines was validated by qRT-PCR and in situ hybridization (ISH). CCK8, colony formation, transwell, wound healing and xenograft experiments were carried out to investigate the function of LINC02320. Antisense oligonucleotide (ASO) was used to target LINC02320. Mass spectrometry, pull-down, western blot and CUT&Tag assays were conducted to investigate the molecular mechanism of LINC02320, ILF2, GRB7, MAPK and FOS.

LINC02320 was highly expressed in metastatic colorectal cancer (CRC) tissues based on RNA-sequencing. ISH staining using tissue microarray (TMA) indicated that LINC02320 is associated with the clinical stage and survival rate of patients with CRC. The results of loss-of-function and gain-of-function experiments demonstrated that LINC02320 facilitates cancer cell proliferation and metastasis in vitro and in vivo while simultaneously inhibiting apoptosis. LINC02320 is present in both the nucleus and cytoplasm, with a nuclear function. Mechanistically, LINC02320 recruits the transcriptional regulator ILF2 to the GRB7 promoter, thereby initiating its transcription. GRB7 then activates the mitogen-activated protein kinase (MAPK) signaling pathway, which contributes to CRC progression and leads to increased phosphorylation of the transcription factor FOS. Phosphorylated FOS directly promotes LINC02320 transcription, forming a positive feedback loop and amplifies this pro-cancer signal. Notably, LINC02320-targeted ASO therapy significantly blocked tumor growth in vivo.

In summary, our findings demonstrate the essential role of LINC02320 involved in CRC progression, which provides novel insights into the importance of lncRNA as a therapeutic target in cancer treatment.

Hepatocellular carcinoma (HCC) is the predominant type of liver cancer with a poor prognosis. Treatment methods include surgery, ablation, liver transplantation, and immunotherapy. Programmed cell death (PCD) plays a significant role in the occurrence and treatment of HCC, and disulfidoptosis, as a novel type of PCD, is associated with tumor prognosis and anti-tumor immunity. The purpose of this study is to explore the role and molecular mechanisms of disulfidoptosis-related genes (DRGs) in the occurrence and development of HCC.

We developed an HCC prognostic signature comprising three DRGs: RPN1, SLC7A11, and GYS1, using the TCGA database. The mRNA expression levels of the signature genes in peripheral blood mononuclear cells (PBMCs) of 196 patients were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the expression of RPN1 in 23 pairs of HCC tissues and adjacent non-tumor tissues were validated by RT-qPCR and immunohistochemistry (IHC). Additionally, the role of RPN1 in HCC was investigated through EdU Assay, CCK8 Assay, wound Healing Test, transwell experiments. The changes of cell cycle were detected by flow cytometry, and the changes of Cyclin (CDK1, CDK2, Cyclin D1, Cyclin E1) were detected by Western blot. We carried out in vivo experiments in a BALB/c nude mice model of HCC established through subcutaneous injection.

RPN1 was significantly upregulated in paired HCC tissues (p < 0.001). HCC group was also significantly higher in PBMCs than healthy group (p < 0.001). Interestingly, RPN1 expression were higher in the HBV group and HBV-LC group than in HBV-HCC group (p < 0.001). IHC experiments confirmed that RPN1 was also up-regulated in HCC tissues (p < 0.05). In vitro experiments showed that knockdown of RPN1 promoted the proliferation and migration of HCC cells, while overexpression of RPN1 inhibited these functions. Flow cytometry and Western blot confirmed that knockdown of RPN1 in HCCLM3 and Huh7 cells resulted in a decrease in the proportion of G0/G1 phase cells and an increase in the proportion of G2/M phase cells. Meanwhile, the expression levels of cell cycle proteins (CDK1, CDK2, Cyclin D1, and Cyclin E1) were significantly elevated. In vivo, overexpression of RPN1 in Hep3B cells can inhibit tumor growth.

In vitro and in vivo experiments confirmed that the overexpression of RPN1 can significantly suppresses the progression of HCC by regulating the cell cycle. RPN1 could potentially serve as a new therapeutic target for HCC.