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Following the publication of the above paper, a concerned reader drew the Editor's attention to the fact that a number of data panels shown for the cell migration assay data in Fig. 1C on p. 1238 and Fig. 3A on p. 1240 appeared to contain overlapping sections, such that data which were intended to show the results of differently performed experiments were apparently derived from a much smaller number of original sources. The authors were contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in this paper, and they have replied to confirm that Figs. 1 and 3 were assembled incorrectly; moreover, although the overlapping images appeared to represent different fields of view, the authors suspected that the errors may have occurred when misfiled images were inserted from the wrong folder during figure preparation. In addition to the issues with Figs. 1 and 3, and even though there were no obvious issues of data mishandling present, the authors also declared that they were unable to retrieve the original experimental data relating to the cell migration assay experiments shown in Fig. 4. The authors requested that the cell migration experiments pertaining to Figs. 1, 3 and 4 be repeated, and the Editor agreed to the authors' request. The revised versions of Figs. 1, 3 and 4, now showing new data for Figs. 1C, 3A and 4B, together with new histograms that have been prepared for the re‑quantification of the new data, are shown on the next two pages. Note that the results obtained from the newly performed experiments were broadly similar to the originally published results, and therefore the revisions made to these three figures have not grossly affected either the results or the conclusions reported in this study. All the authors agree with the publication of this Corrigendum, and they are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 33: 1236‑1242, 2014; DOI: 10.3892/ijmm.2014.1661].

Brain metastases from ovarian cancer are uncommon, with an estimated incidence of 1%-3%, and are usually associated with advanced-stage disease and prolonged survival. We report the case of a 55-year-old woman diagnosed with metastatic high-grade serous ovarian carcinoma presenting with diffuse peritoneal carcinomatosis, pulmonary and lymph node metastases, and an elevated CA-125 level. She received first-line treatment with paclitaxel-carboplatin plus bevacizumab, achieving a marked clinical, radiological, and biological response with normalization of CA-125 levels. Although interval cytoreductive surgery was proposed, the patient declined surgery and further systemic treatment. She was subsequently monitored with serial thoracoabdominal CT scans and CA-125 measurements, and the disease remained clinically, radiologically, and biologically stable for 19 months. The patient then presented with gait disturbance and a right-sided pyramidal syndrome. Contrast-enhanced brain CT revealed 2 large solid-cystic metastatic lesions with extensive vasogenic edema and marked mass effect. Brain MRI confirmed these lesions and identified 2 additional small metastatic lesions that were occult on CT, highlighting the superior sensitivity of MRI for detecting small brain metastases. The patient was treated with corticosteroids followed by whole-brain radiotherapy, resulting in significant neurological improvement. Five-month follow-up contrast-enhanced brain CT demonstrated complete resolution of the cerebellar metastasis and stability of the dominant temporoparietal lesion. This case highlights the diagnostic and therapeutic challenges of isolated brain progression despite stable extracranial disease and normal CA-125 levels, emphasizing the complementary role of MRI and the importance of prompt neuroimaging in ovarian cancer patients presenting with new neurological symptoms.

Ovarian cancer is one of the most lethal malignancies in older adults. The Geriatric Vulnerability Score (GVS) may support treatment decisions in this population. We adapted this score, originally developed in clinical trials, for use with routinely collected geriatric oncology data. Patients aged ≥70 years with FIGO stage III-IV ovarian cancer from the ELCAPA cohort were included. Two versions of the GVS were developed. The modified GVS (0-5 points) included an Activities of Daily Living score (ADL) <6 or an instrumental Activities of Daily Living score (iADL) <8) at diagnosis, a 4-item Geriatric Depression Scale score ≥ 1, lymphocyte count <1 G/L, and serum albumin <35 g/L. The adapted GVS incorporated dependency measures recorded 3 months before diagnosis. The primary endpoint was 2-year overall survival (OS). Eighty-nine patients were included (median age, 81 years). The 2-year OS rate was 51.6% (95% CI 40.3-61.8). Both scores were associated with OS: HR = 1.45 (95% CI 1.07-1.97; p = 0.016; c-index = 0.646) for the modified GVS and HR = 1.72 (95% CI 1.20-2.47; p = 0.004; c-index = 0.664) for the adapted GVS. In multivariable analysis, a Timed Get-Up-and-Go ≥20 s and the adapted GVS were independently associated with OS, improving discrimination (c-index = 0.7522). The GVS can be derived from routinely collected geriatric oncology data. Using dependency measures recorded 3 months before diagnosis slightly improved prognostic performance. Combining the adapted GVS with mobility measures resulted in modestly improved discrimination of mortality risk. Cancer-specific frailty tools may help refine risk stratification and guide treatment decisions in older patients with advanced ovarian cancer.

The family with sequence similarity 3 (FAM3) family has four members (FAM3A, FAM3B, FAM3C, and FAM3D), which have been proven to contribute to tumorigenesis. However, their correlations with ovarian cancer (OV) prognosis and regulatory functions in OV are poorly understood. Here, the expression of four FAM3 family members in OV was analyzed, and functional assays were conducted to explore the effects and underlying mechanisms of FAM3C in OC progression and chemical resistance. FAM3C was upregulated in OV tissues, and higher FAM3C was associated with poorer overall survival and shorter progression-free survival in OV patients. Upregulating FAM3C promoted OV cell proliferation and growth and reduced DNA damage and sensitivity to olaparib. In contrast, downregulating FAM3C restrained OV cell proliferation, promoted DNA damage, and enhanced olaparib sensitivity. Mechanistically, FAM3C overexpression promoted p-STAT3 and HIF-1α expression, which was suppressed after treatment with the HIF-1α inhibitor LW6 or the STAT3 inhibitor static. In vivo assay confirmed that inhibiting STAT3 reversed the FAM3C-mediated promotive effects on tumor growth and enhanced the sensitivity of A2780 cells to olaparib. Taken together, our findings demonstrate that FAM3C promotes OV development and reduces olaparib sensitivity by activating the HIF-1α/STAT3 pathway. FAM3C could serve as a potential diagnostic marker and anticancer target in OV.

Ovarian Cancer is one of the most lethal gynaecological malignancies, particularly due to late-stage diagnosis and high recurrence rate. The high lethality of ovarian cancer stems from a self-sustaining tumor microenvironment driven by metabolic reprogramming and immune suppression, which are the consequences of genomic alterations. Major genomic alterations such as TP53 mutations, amplification of MYC and hyperactivation of PI3K/Akt/mTOR pathway drive the cellular transformation towards aerobic glycolysis, glutamine addiction and anabolic lipogenesis. Additional genomic alterations such as BRCA1/2 deficiency and loss of PTEN enable immune evasion by triggering anti-tumor response via cGAS/STING pathway and recruitment of Myeloid-derived Suppressor Cells. Metabolic dysfunction generates oncometabolites such as lactate and kynurenine that reinforce immune suppression by causing exhaustion of cytotoxic T-cells. The clinical relevance of metabolic and immune combinations has not yet been demonstrated, while PARP inhibitor based strategies have already proven relevant in molecularly selected groups of ovarian cancer patients. Importantly, the number of mechanistic claims discussed in this review is based on preclinical models or on non-ovarian cancer studies, including oncometabolite-mediated immune regulation, the cGAS/STING pathway and metabolic immune crosstalk. Moreover, the clinical studies mentioned encompass both ovarian-cancer-specific trials and larger gynecological and mixed solid-tumor cohorts. Therefore, the conclusions of non-ovarian or early-phase studies should be interpreted as biologically informative and hypothesis-generating and not conclusive evidence of efficacy in ovarian cancer. These mechanisms must be confirmed in future ovarian cancer-specific, biomarker-driven translational studies and prospective clinical trials to see if rational combination strategies can provide durable clinical benefit.

High body-mass index (BMI) defined in the Global Burden of Disease Study as BMI above the theoretical minimum risk exposure level, is an established modifiable risk factor for ovarian cancer, particularly among older women. However, a comprehensive assessment of the global disease burden attributable to high BMI, including its spatiotemporal evolution and underlying drivers, remains lacking, particularly for older women. Using data from the Global Burden of Disease Study 2021, we analyzed disability-adjusted life years (DALYs) and deaths from ovarian cancer attributable to high BMI among women aged ≥55 years from 1990 to 2021. We examined temporal trends, geographic disparities by Socio-Demographic Index (SDI), region, and nation, and performed decomposition analyses to identify contributions from population growth, aging, and epidemiological changes. Globally, the attributable burden increased from 1990 to 2021, with population growth as the main driver. of rising absolute DALYs (86.72) and deaths (85.17). Marked socioeconomic disparities were observed. While high-SDI regions had the highest age-standardized rates in 2021, they showed declining trends., whereas low-middle and low-SDI regions experienced the most rapid increases. Regionally, the fastest increases occurred in South Asia, Southeast Asia, and East Asia, while nationally the largest rises were observed in Timor-Leste, Viet Nam, and Bangladesh. In these settings, epidemiological changes were the dominant contributor to increasing burden. The global burden of ovarian cancer due to high BMI is rising and unequally distributed across SDI regions. While population growth drives the overall increase, escalating obesity prevalence is the key driver in rapidly developing regions. Targeted obesity prevention, improved early detection, and strengthened health-care systems should be prioritized, particularly in high-growth regions. Future studies should improve data quality in low-resource settings and explore cost-effective interventions.

In patients with advanced ovarian cancer, a formidable "drug barrier" formed by interstitial pressure and postsurgical adhesions severely limits the tumor accumulation of intravenously administered chemotherapeutics, leading to sub-therapeutic tumor exposure and inevitable chemoresistance. Injectable short-fiber systems represent a promising localized platform to circumvent the drug barrier; however, their application is limited by poor intratumoral retention of the nanofibers, passive drug release, and a lack of targeting affinity. Here, we present an injectable target-anchoring short nanofiber (TASF) system designed to overcome these multifactorial barriers. TASF integrates a 3D interlocking network for mechanical anchoring, a polydopamine coating for chemical adhesion, folate ligands for tumor-targeted affinity, and an NIR-responsive component for controlled activation. After intratumoral administration, TASF remains stably anchored and is activated by NIR irradiation, triggering rapid drug release and localized photothermal therapy. This design ensures potent chemo-photothermal action is confined to tumor tissues. In ovarian cancer models, NIR-activated TASF treatment downregulates resistance-related protein expression and leads to robust tumor growth suppression. Importantly, the synergistic action of robust adhesion, targeting affinity, and NIR-controlled activation minimizes off-target effects, thereby enhancing the safety profile. This work provides a promising local delivery strategy to circumvent interstitial pressure and stromal barriers that limit drug penetration in solid tumor therapy, offering potential insights for future localized treatment of ovarian cancer.

Most individuals with ovarian cancer (OC) develop cisplatin resistance while undergoing treatment. Bioinformatic analysis has linked DNA Methyltransferase 1 (DNMT1) to chemoresistance development as well as FOXO3a expression in OC patients. In vitro study results revealed cisplatin treatment could induce DNMT1 expression. Knocking down of DNMT1 could decrease the IC 50 of cisplatin. Treatment with cisplatin may reduce FOXO3a expression in OC cells. While in DNMT1 knockdown OC cells, treatment with cisplatin could induce FOXO3a expression. DNMT1 might suppress FOXO3a expression by promoter methylation. FOXO3a overexpression could significantly enhance cisplatin sensitivity. Meta-analysis also revealed opposite effects on OC patients- prognosis: higher expression of DNMT1 is a risk factor for both overall survival and disease-free survival, while high FOXO3a may improve the 5-year survival rate in high-grade serous adenocarcinoma OC patients. Therefore, our results indicated DNMT1 could reduce cisplatin sensitivity in OC cells partially via regulating FOXO3a.

The standard treatment of ovarian cancer involves surgical resection followed by chemotherapy to target residual microscopic tumors. Current chemotherapy is most commonly delivered intravenously (i.v.) because of the toxicity and difficulty in administering intraperitoneal (i.p.) chemotherapy. However, clinical trials have demonstrated that i.p. chemotherapy is superior to i.v. chemotherapy because it can achieve a higher therapeutic concentration and prolonged retention in the peritoneal cavity. To improve the efficacy and safety of i.p. chemotherapy, we developed an injectable hyaluronic acid (HA)-based hydrogel platform for combinatorial and localized delivery of bevacizumab (BVZ), albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) and carboplatin (CPT) in a manner that responds to the high level of matrix metalloproteinases (MMPs) in the i.p. space. HA and dextran sulfate (DS) are chemically modified to allow hydrogels to form with MMP-degradable crosslinkers in less than 1 min upon injection. The in vitro release of BVZ, nab-PTX and CPT is sensitive to MMP concentration and is sustained for up to 28 days. The combined release of BVZ, nab-PTX and CPT from the hydrogels effectively inhibits angiogenesis and tumor cell proliferation in vitro. Moreover, the i.p. administration of the hydrogel system results in tumor burden reduction comparable to the multiple injections of the free drug combination, with reduced systemic side effects. Our work suggests that the injectable MMP responsive hydrogel is a promising i.p. delivery system of BVZ, nab-PTX and CPT to improve i.p. retention and clinical therapeutic effects for ovarian cancer treatment with minimum side effects. STATEMENT OF SIGNIFICANCE: This study presents the first use of hydrogels for intraperitoneal delivery of bevacizumab (BVZ), carboplatin (CPT), and albumin-bound paclitaxel (nab-PTX) to locally treat ovarian cancer. An injectable hyaluronic acid (HA)-based hydrogels platform can be engineered for combinatorial and localized delivery of BVZ, nab-PTX, and CPT in a manner that responds to the high level of matrix metalloproteinases (MMPs) in the intraperitoneal (i.p.) space. HA and dextran sulfate (DS) are chemically modified to allow hydrogels to form with MMP-degradable crosslinkers in less than 1 min upon injection. The combined release of BVZ, nab-PTX and CPT from the hydrogels results in tumor burden reduction comparable to the multiple injections of the free drug combination, with reduced systemic side effects. This work significantly impacts the field of stimuli-responsive biomaterials and cancer therapeutics by offering a robust, modular, and translationally promising drug delivery platform.

To evaluate the association of surgical quality and survival in patients with advanced ovarian cancer in a real-world setting. This population-based registry study analysed FIGO stage III/IV ovarian cancer patients in Hamburg, Germany (2014-2024). Patients were categorized by surgical outcome (no macroscopic residuals vs. macroscopic residuals). Kaplan-Meier functions and Cox proportional hazards models estimated associations with survival outcomes. The cohort comprised 576 patients (median age 65 years, median follow-up 57 months). No macroscopic residuals were achieved in 370 patients (64.2%). In multivariable analysis, no macroscopic residuals were associated with reduced mortality risk (HR 0.62, 95% CI: 0.42-0.90) and reduced progression risk (HR 0.68, 95% CI: 0.49-0.94). Advanced FIGO stage, poor performance status, and increasing age were independent predictors of worse outcomes. Achieving no macroscopic residuals remains a critical prognostic factor in advanced ovarian cancer. The rate of 64.2% demonstrates that optimal surgical outcomes are achievable in routine practice, though opportunities for improvement remain compared to specialized centres.

To systematically validate and compare ultrasonography, using the ultrasound-based International Ovarian Tumor Analysis - Assessment of Different NEoplasias in the adneXa (IOTA-ADNEX) model, with magnetic resonance imaging (MRI), using the MRI-based ADNEX MR scoring system, as second-line imaging modalities for estimating the risk of adnexal malignancy in patients identified as being at risk of malignancy on first-line ultrasound examination. This was a prospective, single-center diagnostic accuracy study designed as a head-to-head comparison. All patients referred to a tertiary referral center at Aarhus University Hospital, Aarhus, Denmark, for suspected adnexal malignancy on first-line imaging between May 2021 and December 2022 were offered second-line diagnostic testing. This comprised both a systematic expert ultrasound examination, including IOTA-ADNEX risk estimation, and a systematic MRI scan with ADNEX MR scores assigned by expert radiologists. The imaging assessments were performed prospectively, with ultrasound examiners and radiologists blinded to the results of other imaging modalities and to the reference standard (tumor outcome). The reference standard was a histopathological diagnosis of the primary adnexal mass or, in a small number of cases, clinical follow-up. Borderline tumors, invasive adnexal malignancy and metastases to the adnexa were grouped as malignancies. Diagnostic performance of the IOTA-ADNEX model, ADNEX MR scoring system and CA 125 for predicting malignancy was evaluated using the area under the receiver-operating-characteristics curve (AUC), and AUCs were compared using DeLong's test. Diagnostic metrics were estimated at clinically relevant cut-offs and scores. Agreement between modalities was assessed for the identification of morphological features and overall risk estimation using Cohen's kappa statistics, intraclass correlation coefficients (ICC) and Bland-Altman plots. For the IOTA-ADNEX model, calibration and the ability to discriminate between tumor subtypes were evaluated. The included cohort comprised 342 patients (342 lesions analyzed). In the final cohort, 78.1% of patients were postmenopausal and the overall prevalence of malignancy was 58.8%. The AUC for distinguishing patients with benign tumors from those with malignant tumors was 0.96 (95% CI, 0.94-0.98) for the IOTA-ADNEX model (with or without CA 125) compared with an AUC of 0.93 (95% CI, 0.91-0.96) for ADNEX MR. Agreement between ultrasound and MRI ranged from moderate to substantial for key morphological features (κ = 0.46-0.75) and from good to excellent for lesion-size measurements (ICC = 0.78-0.92). The IOTA-ADNEX model performed similarly to the ADNEX MR scoring system regardless of lesion morphology or size. The IOTA-ADNEX model had good calibration. Furthermore, its multinomial discriminative ability between tumor subtypes was generally high, although performance was reduced when distinguishing borderline tumors from Stage-I invasive malignancy (AUC, 0.71 (95% CI, 0.56-0.82)). The IOTA-ADNEX model and ADNEX MR scoring system demonstrated comparable diagnostic accuracy for differentiating benign from malignant adnexal masses in this study. Results appeared to be consistent when stratified by lesion morphology. Both modalities may be used for second-line assessment of masses deemed at risk of malignancy in the first-line ultrasound examination, depending on resources in specific centers. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the p16 antibody that the authors reported to have used for the western blot experiment shown in Fig. 4B (cat. no. ab51243) is specific for the protein known as P16 ARC (or ARPC5), not the apoptosis‑associated protein p16INK4a, as was intended. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that western blot data featured in Fig. 5 were strikingly similar to data that had already been published in a different paper in the journal Oncotarget that featured no authors in common, and western blot data included in Fig. 1B were also very similar to data in another article, which again featured no authors in common ,that was submitted around the same time to the journal OncoTargets and Therapy . Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 5097‑5104, 2019; DOI: 10.3892/mmr.2019.10212].

This multicenter, randomized, open-label, exploratory Phase 2 trial assessed SHR-2004, an anti-FXI antibody, for venous thromboembolism (VTE) prevention in patients undergoing ovarian cancer surgery-a population at particularly high thrombotic risk conducted at 25 sites in China. Patients with newly diagnosed Stage III-IV or recurrent ovarian cancer scheduled for surgery were randomly assigned (1:1) to receive subcutaneous SHR-2004 (180 mg on Day 1 and 120 mg on Day 15) or enoxaparin-rivaroxaban (subcutaneous enoxaparin 40 mg once daily during hospitalization, followed by oral rivaroxaban 10 mg once daily after discharge until Day 28). The primary efficacy outcome was the composite of VTE events within 28 days. The primary safety outcome was major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) from first dose to 28 days. Between February 19, 2024 and September 17, 2024, 198 patients received assigned treatment (90 with SHR-2004, 108 with enoxaparin-rivaroxaban) and were included in the safety analysis. Among 181 patients who completed protocol-mandated ultrasonography, VTE occurred in 11 (12.6%) patients in the SHR-2004 group and 19 (20.2%) in the enoxaparin-rivaroxaban group (difference -8.4%, 95% CI -19.9 to 3.1) by Day 28. MB/CRNMB rates were similar between groups (SHR-2004: 2/90 [2.2%]; enoxaparin-rivaroxaban: 2/108 [1.9%]). In this study, SHR-2004 showed comparable efficacy to enoxaparin-rivaroxaban for preventing postoperative VTE in patients undergoing ovarian cancer surgery, with a similar low risk of MB or CRNMB. The twice-monthly dosing schedule offers a potential advantage over daily anticoagulation, supporting further investigation in adequately powered Phase 3 trials. Trial Registration: ClinicalTrials.gov identifier: NCT06220123.

Ovarian cancer is the gynecological malignancy with the highest mortality rate. Platinum resistance remains a major clinical challenge, severely limiting the therapeutic efficacy of cisplatin-based chemotherapy. In recent years, nanomedicine delivery systems have emerged as a promising strategy to enhance the efficacy of conventional cancer treatments. Herein, we constructed a multifunctional graphene oxide-based nanoplatform by functionalizing graphene oxide with hyaluronic acid, gold nanorods, and indocyanine green, followed by loading of cisplatin to form GO-HA-GNRs-ICG@Pt. This nanoplatform exhibits remarkable photothermal and photodynamic conversion efficiency, active tumor-targeting capability, and pH/near-infrared light dual-responsive cisplatin release. More importantly, in vitro and in vivo studies demonstrate that GO-HA-GNRs-ICG@Pt achieves significantly higher therapeutic efficacy and better biosafety compared to cisplatin monotherapy in A2780 ovarian cancer cells. Mechanistically, we discovered that GO-HA-GNRs-ICG@Pt activates the ROS-PINK1/Parkin-mediated mitophagy signaling axis, ultimately enhancing the cisplatin sensitivity of ovarian cancer cells. This work not only provides a theoretical foundation for the development of targeted multifunctional nanoplatforms for integrated cancer therapy but also offers a new synergistic treatment strategy with potential for addressing drug resistance in clinical ovarian cancer.

Breast cancer is the most common malignant tumor in women. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for classification and treatment. A subgroup with HER2-low expression has been identified, but existing evidence is heterogeneous. This systematic review and meta-analysis compared pathological response and survival outcomes between HER2-low and HER2-zero early-stage breast cancer to clarify prognostic features. This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251120506). PubMed, Embase, Web of Science, ClinicalTrials.gov, and major oncology conferences were searched through September 2025. Cohort studies of early-stage breast cancer comparing HER2-low (IHC 1+/2+ and ISH-negative) vs. HER2-zero with extractable pCR, DFS, or OS data were included. Studies involving HER2-positive patients or inconsistent definitions were excluded. Meta-analyses were performed using RevMan 5.3. Twenty-eight studies involving 115,182 patients were included. HER2-low patients showed significantly lower pCR rates (OR = 0.58, 95% CI: 0.52-0.65). DFS favored HER2-low (multivariate HR = 0.75, 95% CI: 0.69-0.83), especially in HR+ tumors, with a weaker effect in HR- cases. OS also favored HER2-low (HR = 0.80, 95% CI: 0.72-0.89), mainly driven by the HR- subgroup; no OS difference was seen in HR+ tumors. Sensitivity analyses and funnel plots indicated robust results with no apparent publication bias. Overall study quality was high (17 high-quality, 11 moderate-quality). HER2-low early breast cancer shows lower pCR after neoadjuvant therapy but better long-term survival. These findings support the clinical relevance of HER2-low as a biologically meaningful subgroup within HER2-negative disease, while its status as a stable and independent subtype still requires further validation through prospective studies, standardized testing, and multi-omics investigation.

Triple-negative breast cancer (TNBC) presents a serious therapeutic challenge, largely owing to its metabolic adaptability and the immunosuppressive nature of its tumor microenvironment (TME). Photodynamic therapy (PDT) can cause oxidative injury and induce immunogenic cell death (ICD); however, its antitumor activity is often limited by inadequate reactive oxygen species (ROS) accumulation and weak immune activation. To address these barriers, a supramolecular self-assembled nanoplatform, termed OC@cRGD, was constructed through the co-assembly of the fatty acid synthase (FASN) inhibitor orlistat and the photosensitizer chlorin e6 (Ce6), followed by cyclic RGD (cRGD) modification to support integrin-mediated tumor targeting. This self-assembled design allows high drug loading and links metabolic interference with redox stress in a single nanoscale formulation. At the mechanistic level, orlistat disturbs lipid homeostasis and reduces the saturated fatty acid-based protection that helps TNBC cells resist membrane peroxidation. In parallel, light-activated PDT delivers a spatially restricted oxidative burst. After laser irradiation, these two processes act together to drive extensive iron-dependent lipid peroxidation, along with reduced GPX4 and FASN expression, thereby increasing cellular susceptibility to ferroptosis. This ferroptosis-reinforced PDT further induces pronounced ICD. In 4T1 tumor-bearing mice, OC@cRGD combined with laser irradiation inhibited tumor growth and reshaped the immune microenvironment, as reflected by dendritic cell maturation, M1-like macrophage polarization, and increased CD8 + T-cell infiltration. Overall, this study combines metabolic intervention with photoimmunotherapy and offers a metabolism-guided strategy for the development of self-assembled nanotherapeutics.

The development of antibody‑drug conjugates (ADCs) is reshaping human epidermal growth factor receptor (HER)2 expression stratification and treatment decision‑making in breast cancer. HER2‑low and HER2‑ultralow breast cancers were previously included largely within the conventional HER2‑negative category. However, newer HER2‑targeted ADCs, represented by trastuzumab deruxtecan, have created therapeutic opportunities for these patients and have moved HER2 assessment beyond a binary 'positive/negative' model toward a more refined, continuum‑based stratification system. Even so, HER2‑low and HER2‑ultralow breast cancers should not be regarded as stable or independent molecular subtypes. They should be understood as treatment‑relevant states marked by low target density, spatial heterogeneity, temporal variation and diagnostic uncertainty. Although clinical studies have shown that HER2‑targeted ADCs can improve outcomes in some patients with low HER2 expression, several challenges still limit durable benefit. These include primary resistance, acquired resistance, limited ability to predict which patients will benefit and unclear combination or sequencing strategies after progression on ADC therapy. The present review summarized the biological basis, resistance mechanisms and potential counterstrategies of ADC therapy in HER2‑low and HER2‑ultralow breast cancer. In tumors with low HER2 expression, ADC resistance may arise from multiple interacting factors, including decreased or lost HER2 expression, spatial heterogeneity of target distribution, impaired ADC delivery and intracellular processing, reduced payload sensitivity, enhanced DNA damage repair, tumor microenvironment‑related barriers and biases caused by pathological interpretation and sampling. To address these mechanisms, future therapeutic optimization should move beyond single‑agent selection and toward mechanism‑guided combination therapy, rational sequencing of ADCs with different targets or payloads and the design of next‑generation ADCs. Precision treatment for HER2‑low and HER2‑ultralow breast cancer should also rely on more than HER2 immunohistochemistry alone. Dynamic reassessment, digital pathology, liquid biopsy, multi‑omics biomarkers and prior treatment exposure should be integrated to build multidimensional predictive models. Such models may improve patient selection, strengthen resistance identification and support longer‑term therapeutic benefit.

[This corrects the article DOI: 10.3892/ol.2017.6025.].

Women who develop breast cancer at the age of 40 years or younger often face considerable barriers to fertility preservation services. This systematic review and meta-analysis examined global fertility preservation utilization rates and the factors associated with uptake. To synthesize the evidence on (1) global fertility preservation utilization rates and (2) factors associated with fertility preservation uptake among young breast cancer patients. We systematically searched five databases (PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO) and trial registries for studies published from January 2010 to August 2026 involving women aged 40 years or younger with breast cancer. Proportions and odds ratios (ORs) were pooled using random-effects meta-analysis, and heterogeneity was assessed with the I 2 statistic. The certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eighteen studies (n = 13,394) were included. The pooled fertility preservation utilization rate was 26.8% (95% CI: 20.0-34.1%; I 2 = 98.8%). Regional estimates differed widely (Europe 47.8%; Asia 19.8%; North America 14.0%), but the North American estimate was highly imprecise (95% CI: 5.0-26.6%; I 2 = 99.3%), so regional comparisons should be interpreted with caution. Older age within the young-patient range (OR 0.71), higher educational attainment (OR 1.58), being partnered (OR 1.74), nulliparity (OR 2.12), and insurance coverage (OR 2.85) were associated with uptake, with specialist referral the strongest enabling factor (OR 4.26). The certainty of evidence was rated low to very low across outcomes. Access to fertility preservation appears inequitable worldwide, although substantial heterogeneity and imprecision in some regional estimates preclude definitive cross-regional rankings. Younger age, higher education, partnership status, and insurance coverage were associated with fertility preservation uptake. Because the evidence is observational and heterogeneous, causal inferences should be drawn with caution. Policy reforms supporting insurance coverage and standardized training may improve access to fertility preservation, but further high-quality research is needed.

Venous thromboembolism (VTE) is a serious complication for breast cancer (BC) survivors. We identified records of female BC survivors from the Korean Health Insurance Service database between January 1, 2010, and December 31, 2016. After applying exclusion criteria (age < 18 years, prior cancers or VTE, absence of BC surgery, or missing data), 112,522 BC survivors were included; for the comparison group, BC survivors were matched (1:3) to women without cancer history. VTE risk was evaluated with a Fine and Gray model, accounting for death as a competing risk; multiple time periods were analyzed. Associations between VTE risk and treatment modalities also were estimated. Over a mean analysis period of 7.4 years, BC survivors had 3621 VTE events; their subdistribution hazard ratio (sHR) for VTE was greater than that of the comparison group (sHR 1.68, 95% CI 1.61-1.75). The risk was prominent within the first year post-diagnosis (sHR 7.78, 95% CI 6.88-8.80) and attenuated in analyses restricted to VTE events occurring beyond 1 year after diagnosis (sHR 1.34, 95% CI 1.28-1.40), but remained significantly elevated in landmark (delayed-entry) analyses starting at later time points. Anthracycline (sHR 1.11, 95% CI 1.00-1.23) and taxane (sHR 1.73, 95% CI 1.57-1.91) therapies were associated with an increased risk of VTE in 1-year landmark analysis. Female BC survivors are at increased risk of VTE, especially during the first year post-diagnosis, which underscores the importance of VTE risk assessment for BC survivors.

[This corrects the article DOI: 10.3892/ol.2015.3646.].

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by an immunosuppressive tumor microenvironment and resistance to chemotherapy. Previous studies have indicated that apolipoprotein C-II (APOC2) is involved in the immune microenvironment of several malignancies and is upregulated in breast cancer; however, the molecular mechanisms through which APOC2 regulates the immune microenvironment in TNBC remain poorly understood. In the present study, we found that APOC2 was upregulated in TNBC tissues and was negatively correlated with M1 macrophage infiltration. APOC2 overexpression in 4 T1 cells promoted tumor progression by enhancing cell proliferation, migration, and invasion, while suppressing M1 macrophage polarization. In addition, KLHL1, a substrate adaptor for the Cullin3-RING E3 ubiquitin ligase complex, was found to interact with APOC2, and KLHL1 overexpression reversed the biological effects induced by APOC2. Mechanistically, KLHL1 promoted APOC2 protein degradation through the ubiquitin-proteasome pathway, thereby enhancing M1 macrophage polarization and suppressing the malignant behavior of tumor cells. Finally, in vivo xenograft experiments demonstrated that APOC2 reduced M1 macrophage polarization and increased tumor weight and volume, whereas KLHL1 overexpression counteracted the oncogenic effects of APOC2. Collectively, these findings reveal that activation of the KLHL1/APOC2 axis enhances M1 macrophage polarization and inhibits TNBC progression, providing novel insights into the immune regulatory mechanisms underlying TNBC development.

Endocrine therapy has stood as a fundamental pillar in addressing hormone receptor-positive breast cancer. Nevertheless, the emergence of resistance to these therapies poses a significant and ongoing clinical hurdle. Of late, there is a growing interest toward investigating the role of steroidal molecules in treatment of endocrine resistant breast cancer. The intricate and fascinating structural framework of the steroidal nucleus has drawn considerable scientific attention globally to devise novel and effective derivatives for combating breast cancer. Apart from its structural appeal, the multi-target oriented steroidal nucleus empowers researchers to design and develop a wide range of compounds for use in the treatment of breast cancer. Steroids remain a cornerstone of breast cancer clinical setting, offering significant advantages over non-steroidal counterparts as they act through multiple mechanisms like irreversibly inactivating the aromatase enzyme, downgrading estrogen receptors and simultaneously reducing estrogen and androgen levels through sulfatase inhibition. It is implied that the development of novel multifunctional steroidal molecules with complementary mechanisms could positively transform hormone-dependent cancer therapy by ensuring prolonged estrogen suppression and reduced resistance risk. This comprehensive review article provides an overview of the underlying complex mechanisms responsible for the development of resistance to endocrine therapies. Furthermore, it aims to explore the potential therapeutic possibilities that steroidal molecules may offer within this resistant context.

Triple-negative breast cancer (TNBC) lacks effective therapeutics in clinical practice. Sorting nexin 10 (SNX10) plays essential roles in various cancers, and the role of SNX10 in TNBC remains unknown. This study investigated the role and action mechanism of SNX10 in TNBC. Using the Kaplan-Meier Plotter database and bc-GenExMiner database to analyze the SNX10 expression and clinical significance. Functional assays, including MTT, colony formation, transwell assays, and xenograft experiments, were used to evaluate the role of SNX10 in TNBC. The GeneChip PrimeView Human Gene Expression Array was used to determine the downstream targets and pathways. Cholesterol levels and the expression of enriched cholesterol synthesis genes were detected by Filipin assay, RT-PCR, and Western Blot. The relationship of SNX10 and cholesterol biosynthesis was confirmed using CO-IP and immunofluorescence staining assays. SNX10 is positively related to poor prognosis of breast cancer and markedly up-regulated in TNBC. Knockdown of SNX10 suppressed cell proliferation, migration, and invasion, and slowed the tumor growth in vivo . Mechanistically, SNX10 positively regulates the content and distribution of cellular cholesterol, as does the expression of enriched cholesterol synthesis genes, and SNX10 interacts with SREBP2 and prolongs its half-life. Blocking with lovastatin, cholesterol, or siSREBP2 reversed these effects caused by altering SNX10 in TNBC cells in vitro . SNX10 promoted TNBC progression through the regulation of cholesterol biosynthesis, which was mediated by interaction with SREBP2 and maintenance of its stability. SNX10 may be an effective therapeutic target for TNBC, and our study provides new insights into therapeutic strategies.

Reliable biomarkers for predicting neoadjuvant chemotherapy (NAC) response in triple-negative breast cancer (TNBC) remain limited. We explored whether RecurIndex-derived molecular features were associated with total pathological complete response (tpCR). Seventy-four patients with TNBC treated with dose-dense NAC were analyzed. Associations between RecurIndex risk scores, 18 core genes, and tpCR were assessed using logistic regression and ROC analyses. Clinical-molecular models were internally validated by bootstrap resampling. Public single-cell RNA-seq data were used for biological contextualization. Twenty-nine patients (39.2%) achieved tpCR. The distant recurrence score, was significantly associated with tpCR. OBSL1, BLM, and CCR1 were identified as candidate tpCR-associated genes. The model combining OBSL1, BLM, and clinical nodal stage achieved an AUC of 0.838 and an optimism-corrected AUC of 0.799. RecurIndex-derived molecular features were associated with tpCR in TNBC. These exploratory findings warrant validation in independent cohorts.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer with high brain metastatic (BM) potential. Tumor-derived exosomes are implicated as key modulators during the formation of the pre-metastatic niche (PMN). However, the regulation of TNBC-BM-derived exosomes on brain PMN remains enigmatic. The morphology and uptake of exosomes were identified using transmission electron microscopy and live-cell imaging, respectively. Differentially secreted miRNAs and mRNA were identified using high-throughput sequencing. The permeability of the blood‒brain barrier (BBB) and tight junction integrity were examined using immunofluorescence staining. Cell viability was examined using the CCK-8 assay. The apoptosis and intracellular ROS were investigated using fluorescence staining. The expression of mRNAs was examined using qPCR. miR-103b was significantly increased in exosomes derived from TNBC-BM cells. miR-103b compromised the tight junctions of HUVECs and increased BBB permeability in mice. Additionally, miR-103b promoted apoptosis and increased intracellular ROS in HUVECs and U251 cells, two cell lines commonly used as surrogates for brain microvascular endothelial cells and astrocytes, respectively. miR-103b-regulated differentially expressed genes modulated tight junction, apoptosis, oxidative stress, inflammation, and metabolism. Target analysis identified 216 targets of miR-103b, among which hub targets were associated with biological processes involved in maintaining the BBB and the glucose metabolism signaling pathway. Collectively, our findings for the first time reveal that exosomal miR-103b from TNBC-BM cells potentially regulates the two major cellular constituents of the brain PMN, highlighting its role in the formation of the brain PMN during TNBC-BM and its potential as a promising therapeutic target.

Triple-negative breast cancer (TNBC) remains one of the most lethal breast cancer subtypes, driven by early dissemination and resistance to therapy. Here, we reveal a macrophage-centered cytokine circuit that fuels TNBC metastasis and immune evasion. Tumor cells reprogram naïve macrophages into tumor-associated macrophages (TAMs) that secrete CCL3, CCL4, CXCL2, and IL-1β, collectively promoting epithelial-to-mesenchymal transition, migration, transendothelial invasion, and lung colonization. These TAMs, in turn, convert naïve CD4⁺ T cells into FOXP3⁺ Tregs, establishing a self-reinforcing immunosuppressive niche. Pharmacological inhibition of CCR5, CXCR2, and IL1R1 with maraviroc, navarixin, and anakinra, respectively, disrupted this cytokine axis, suppressing metastatic colonization in vivo . Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.

Triple-negative breast cancer is an aggressive and heterogeneous breast cancer subtype for which immune checkpoint inhibitors combined with chemotherapy have improved outcomes in selected patients. However, primary and acquired resistance remain common, underscoring the need to identify extrinsic, modifiable determinants of antitumor immunity. Increasing evidence indicates that the gut and tumor-associated microbiota shape systemic and intratumoral immune tone and influence the efficacy of cancer therapies. Beyond microbial composition, microbiota-derived metabolites-including short-chain fatty acids, indole-tryptophan derivatives, bile acids, polyamines, and other small molecules-can act as functional mediators linking microbial ecology to immune-cell programming and tumor biology. These metabolites modulate dendritic cell function, T-cell priming and fitness, myeloid polarization, inflammatory set points, and metabolic pathways within the tumor microenvironment, thereby potentially enhancing or constraining responses to chemoimmunotherapy. Importantly, while some studies propose intratumoral microbial effects, most clinically actionable evidence currently supports systemic gut-derived metabolites and immune tone modulation that secondarily shapes the TNBC tumor microenvironment. In this review, we synthesize current knowledge on (i) the immunobiology of triple-negative breast cancer (TNBC) relevant to microbiota-driven modulation, (ii) mammary and gut microbiome features reported in TNBC, and (iii) mechanistic pathways through which microbial metabolites may regulate antitumor immunity and immune checkpoint inhibitors (ICI) sensitivity. We also discuss methodological considerations for integrating microbiome profiling with metabolomics and immune phenotyping and evaluate emerging opportunities to leverage microbiota-derived metabolites as biomarkers and therapeutic targets. Finally, we highlight translational strategies-including diet, pre/probiotics, antibiotic stewardship, fecal microbiota transplantation, and metabolite-centric ("postbiotic") approaches-and outline priorities for TNBC-focused, prospective multi-omics studies to move from associative signatures toward actionable interventions.