Breast cancer is the most common malignancy, with approximately ∼20% of cases involving HER2 overexpression. Trastuzumab deruxtecan (T-DXd), an HER2-targeted antibody-drug conjugate, is approved for HER2-high and HER2-low disease. This meta-analysis assessed four randomized controlled trials (DESTINY-Breast02, -03, -04, and -06; 2555 patients) from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. A random-effects model revealed that T-DXd significantly improved progression-free survival (hazard ratio [HR] = 0.433; 95% confidence interval [CI]: 0.305-0.616; P < 0.001; = 90.7%) and overall survival (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001; = 0%) versus control regimens, with consistent benefits across HER2 subgroups. However, T-DXd increased the risks of interstitial lung disease (relative risk [RR] = 13.832; P < 0.001), decreased left ventricular ejection fraction (RR = 2.247; P < 0.001), anemia, nausea, vomiting, decreased appetite, and alopecia; neutropenia and diarrhea risks were comparable between groups. These findings highlight T-DXd's survival benefits and toxicity profile warranting monitoring.

ROS1 gene fusions are oncogenic driver in 1-2% non-small cell lung cancer (NSCLC). This report presents the first case of a novel SNX25-ROS1 fusion mutation in a 56-year-old female with lung adenocacinoma, presenting with headaches and behavioral changes. Imaging revealed a primary tumor in the lung and metastasis to lymph nodes, brain, and bones. Histopathological examination confirmed the diagnosis of lung adenocarcinoma, classified as cT3N3M1 (Stage IV). Next-generation sequencing identified a previously unreported SNX25-ROS1 fusion mutation. A fusion was identified in exon 1 of the SNX25 gene and exon 31 of the ROS1 gene. The fusion occurs within ROS1 intron 31, and the complete kinase domain is retained. Based on this finding, the patient was initiated on targeted therapy with entrectinib. Follow-up imaging at six months demonstrated significant reduction in the primary lung tumor size, regression of metastatic lesions, and resolution of intracranial edema. The patient exhibited marked clinical improvement with no significant treatment-related adverse events. This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.

Polymer-based nanoparticles (PNPs) are emerging as a cornerstone in cancer therapy due to their ability to enhance drug solubility, improve pharmacokinetics and achieve precise tumor targeting. Nanoparticles, encompassing liposomes, dendrimers, and metallic particles, include typical characteristics such as improved surface area, regulated release and the capacity to encapsulate diverse therapeutic compounds augmenting the pharmacokinetics and bioavailability of anticancer drugs. Recent studies demonstrate drug loading efficiencies of 80-90%, circulation half-life extensions of 2-5 fold, and tumor accumulation improvements of 3-10 times compared to free drugs. FDA-approved formulations such as Abraxane (albumin-bound paclitaxel) and clinical candidates like Genexol-PM (polymeric micelles) highlight the translational relevance of PNPs. This review consolidates advancements in polymeric nanocarriers, including nanospheres, nano-capsules and hybrid composites, while addressing limitations in regulatory approval and personalized oncology integration. This study shows that nanoparticle-based cancer therapeutics hold immense potential to improve treatment efficacy and patient outcomes in clinical oncology.

While targeted therapies have remarkably transformed the landscape of lung adenocarcinoma (LUAD) management, the clinical implications of concurrent mutations in EGFR and ERBB2 remain inadequately understood due to their exceptional rarity in patients. This lack of understanding leads to significant uncertainty regarding therapeutic strategies for individuals with such co-mutations, as neither single-agent EGFR tyrosine kinase inhibitors (TKIs) nor HER2-targeted therapies have demonstrated established efficacy in this specific molecular context. Here, we present a compelling case involving a 61-year-old female patient diagnosed with advanced LUAD, with both EGFR L858R (exon 21) and ERBB2 S310F mutations identified through comprehensive next-generation sequencing (NGS). The patient received a treatment regimen consisting of the third-generation EGFR TKI furmonertinib, combined with localized radiotherapy, which resulted in a marked and significant clinical response. Our findings indicate that furmonertinib may effectively address the therapeutic uncertainties associated with EGFR/ERBB2 co-mutations, presenting a promising clinically actionable strategy while we continue to await the advent of more personalized and tailored treatment solutions.

Nasopharyngeal carcinoma (NPC) is a radiosensitive malignancy, but chemotherapy resistance remains a major challenge. This study investigated the role of RACGAP1, a GTPase regulator often overexpressed in cancers, in NPC progression and chemoresistance. We observed significantly elevated RACGAP1 levels in NPC cell lines compared to normal nasopharyngeal epithelial cells. Functional experiments demonstrated that silencing RACGAP1 effectively inhibited cell proliferation and colony formation, promoted apoptosis, and enhanced cisplatin sensitivity-evidenced by lower IC50 values and increased drug-induced apoptosis. Mechanistically, these antitumor effects were linked to inhibition of HIF-1α signaling. Importantly, restoring HIF-1α expression partially reversed the phenotypic changes caused by RACGAP1 knockdown. In summary, our findings establish that RACGAP1 promotes malignant progression and confers cisplatin resistance in NPC by upregulating HIF-1α, suggesting the RACGAP1/HIF-1α axis as a promising therapeutic target to overcome chemoresistance.

Cyclophosphamide is a chemotherapeutic agent widely used in breast cancer management. As a prodrug, its therapeutic efficacy and toxicity are profoundly influenced by host genetic variations that govern its metabolism, detoxification, DNA repair, and cellular transport mechanisms. This review examines pharmacogenomic landscape of cyclophosphamide in breast cancer, with focus on key genes and polymorphisms. A comprehensive literature review was conducted to identify genetic variants affecting cyclophosphamide metabolism (CYP2B6, CYP3A4, CYP3A5, CYP2C9, and CYP2C19), detoxification (ALDH1A1, GSTM1, GSTT1, and GSTP1), DNA repair (XRCC1, ERCC1, ERCC2, and MGMT), and transport (ABCB1 and SLCO1B1). Clinical correlations with drug response and adverse effects were analyzed. Polymorphisms in CYP2B6 (6, 9) and CYP3A5 (3) significantly alter activation and systemic exposure. Null variants in GSTM1 and GSTT1 are linked to increased drug toxicity due to impaired detoxification. DNA repair gene variants, such as XRCC1 Arg399Gln and ERCC2 Lys751Gln, influence treatment response and risk of side effects.

Glioblastoma is an aggressive brain tumor with median survival under 2 years despite standard therapy. At recurrence, treatment options are limited, and regorafenib has emerged as a promising option. A systematic search was conducted through Pubmed, Cochrane Library, Embase, and Web of Science for studies on regorafenib in adult recurrent glioblastoma, and a single-arm meta-analysis with random-effects model was performed to pool the data. Across ten studies (724 patients), median overall survival (OS) was 7.2 months and median progression-free survival (PFS) was 2.6 months, with a 12-month OS of 22.5% and a 6-month PFS of 14.9%. Disease control rate (DCR) was 36.1%, including stable disease (SD) of 26.6% and a partial response of 8.5%; progressive disease occurred in 60.9%, and grade 3-4 adverse events in 31.4%. Meta-regression suggested MGMT methylation was associated with improved OS, PFS, DCR, and SD, while male sex was associated with better OS and SD. Overall, regorafenib demonstrated a predictable safety profile in recurrent glioblastoma, with outcomes potentially improved in male patients with MGMT-methylated tumors.

Bladder cancer is a prevalent and lethal malignancy worldwide, with treatment options often limited by the development of chemoresistance, especially to cisplatin-based regimens. In this study, we identified ubiquitin-specific protease 54 (USP54) as a novel regulator of bladder cancer cell proliferation, stemness, and cisplatin resistance. USP54 expression was consistently downregulated in both clinical bladder cancer specimens and cell lines. Functional experiments demonstrated that USP54 overexpression inhibited cancer cell growth, attenuated CSC-like properties, and restored cisplatin sensitivity in resistant cells by promoting drug-induced apoptosis. Mechanistically, USP54 directly interacted with SIRT6 and facilitated its deubiquitination, leading to increased SIRT6 protein stability. This post-translational stabilization of SIRT6 was shown to mediate the tumor-suppressive functions of USP54 in bladder cancer progression and chemoresistance. Together, these results uncover the USP54-SIRT6 axis as a previously unrecognized regulatory pathway controlling stemness and cisplatin response in bladder cancer.

Teicoplanin is a glycopeptide antibiotic with a long elimination half-life (50 hours) that allows administration thrice a week, though it is approved for daily use. The aim of this retrospective, single-arm study is to assess the clinical outcome of using thrice-weekly teicoplanin (TWT) as outpatient parenteral antibiotic therapy (OPAT) for deep (DSIs) and non-deep-seated infections (NDSIs). We included 37 outpatients (25 with DSIs and 12 with NDSIs) treated with TWT between 01/2021 and 10/2023. The outcome was favorable in 78% of them (80% with DSI, 75% with NDSIs) and Therapeutic drug monitoring (TDM) was performed in all cases. 8 patients required dosage modification because of inadequate trough levels; they were younger and had a higher creatinine clearance. 6/37 patients experienced adverse events, mostly skin rash (4/6). TWT can be a good option for OPAT; its pharmacokinetic reduces the number of hospital accesses and TDM permits to tailor the dosage.

Erdheim-Chester Disease (ECD) is a rare, multisystemic histiocytosis with complex diagnosis and management. We report a case of a 44-year-old male with ECD,confirmed by lung biopsy, presenting with persistent fatigue, intermittent low-grade fever, and bilateral interstitial lung disease. The patient initially received vincristine and prednisone, followed by maintenance therapy with 6-mercaptopurine, which resulted in both symptomatic and radiographic improvement. However, disease progression was noted after six months. Second-line therapy using a cytarabine-based regimen adapted from the Japan LCH Study Group-02 protocol achieved sustained remission for over two years. This case highlights the diagnostic complexity and therapeutic challenges of pulmonary-predominant ECD. It further underscores the potential utility of sequential cytotoxic chemotherapy as an alternative strategy in settings where targeted therapies, such as BRAF inhibitors, are not accessible. Future studies are needed to validate the role of such regimens in broader ECD populations.

This study aimed to evaluate the efficacy and prognostic factors of GEMOX (gemcitabine and oxaliplatin) combined with Tislelizumab in patients with advanced Gallbladder cancer (GBC). 150 patients with stage III-IV GBC were divided into two groups: 88 received GEMOX alone, and 62 received GEMOX combined with Tislelizumab. Clinical characteristics, treatment responses, progression-free survival (PFS), overall survival (OS) and adverse events were analysed. The combination group showed improved median OS (13.35 vs. 10.26 months, HR = 0.530, 95% CI: 0.357-0.786) and PFS (7.28 vs. 5.18 months, HR = 0.393, 95% CI: 0.278-0.555). The disease control rate (DCR) and objective response rate (ORR) were significantly higher in the combination group (DCR: 83.87% vs. 67.05%, P = 0.021; ORR: 40.32% vs. 20.45%, P = 0.008). Multivariate analysis identified TNM stage, CA19-9 status, CPS score, tumour diameter, and lesion multiplicity as independent prognostic factors for OS. GEMOX combined with Tislelizumab may improve survival outcomes in patients with advanced GBC.

The aim of this Phase 1, multicentre, open-label study was to evaluate the safety, tolerability and pharmacokinetics (PK) of abemaciclib administered at global recommended Phase 2 dose (RP2D) of 200 mg twice daily, combined with standard doses of abiraterone and prednisolone, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Dose-limiting toxicities (DLTs) were assessed for 28 days post-first dose. Six patients were treated, and all experienced at least one treatment-emergent adverse event (TEAE), mostly low grade; no Grade 4 or 5 TEAEs occurred. Diarrhoea was the most common TEAE (all events were Grade 1 except for one Grade 2). Three patients experienced serious adverse events (SAEs), leading to treatment discontinuation in two cases. The PK profile was consistent with non-Japanese patients, with no PK drug-drug interactions detected. The study confirms that the global RP2D of abemaciclib is suitable for Japanese patients with mCRPC treated with abiraterone and prednisolone.

Well-differentiated (WDLPS) and dedifferentiated liposarcomas (DDLPS) are subtypes with distinct behaviors, often driven by CDK4 amplification. While CDK4/6 inhibitors such as palbociclib show promise in trials, real-world data are scarce.

The study aimed to compare the impact of combination and monotherapy on mortality, antibiotic consumption using 'Days of Therapy (DOT)', and antibiotic-related adverse events in patients with methicillin-susceptible (MSSA) bacteraemia.

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 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 rise of immunotherapies, particularly PD-L1 inhibitors like avelumab, has advanced cancer care, but its pulmonary safety profile remains unclear. Using FAERS data from 2013-2023, we evaluated respiratory complications linked to avelumab through disproportionality analysis with OpenVigil 2.1. Several significant associations emerged: bacterial pneumonia (ROR 6.79, 95% CI 2.19-21.10, n=3), pneumonitis (ROR 4.37, 95% CI 1.96-9.74, n=6), respiratory failure (ROR 3.99, 95% CI 2.31-6.90), pulmonary edema (ROR 3.40), respiratory distress (ROR 3.31), and pulmonary embolism (ROR 2.87). By contrast, non-specific pneumonia (ROR 0.97) and dyspnea (ROR 0.97) showed no signal. These results suggest avelumab may predispose to specific severe pulmonary toxicities. Clinicians should monitor for early respiratory compromise, with prospective studies warranted to clarify causality and preventative strategies.

To explore the clinical characteristics of diabetes mellitus (DM) induced by atezolizumab in cancer patients and provide evidence to guide the rational clinical application of atezolizumab. We conducted a retrospective study on diabetes induced by atezolizumab, analyzing it by retrieving the case reports in the database from 2016 to 8 April 2025. Overall, the median age of the 30 atezolizumab induced DM patients was 67 years (44-85 years), among which 19 patients (63.3%) were male. Atezolizumab induced DM occurred at a median of 147 days (15-600 days) after the treatment with atezolizumab. 12 patients (40.0%) had ICI-T1DM, 10 patients (33.3%) had ICI-FT1DM, 8 patients (26.7%) had ICI-DM. The HLA typing test information provided by 10 patients showed that these patients carried susceptible genes related to DM. After DM was induced by atezolizumab, insulin or a combination of insulin and oral hypoglycemic agents was used, achieving a good effect in blood glucose levels. 10 patients (33.3%) continued to use atezolizumab after glycemia improvement. Among the 30 patients, except for 4 patients who died due to tumor progression (3 cases) and liver injury (1 case), the rest all alive or not reported their survival status. In conclusion, when administering atezolizumab treatment for cancer patients, it is recommended to monitor blood glucose levels regularly. In case atezolizumab induced DM occurs, insulin should be administered to regulate blood glucose.

Mal, T cell differentiation protein 2 (MAL2) has emerged as a potential regulator in the progression of bladder cancer (BCa). Therapeutic resistance to sunitinib poses a significant challenge in BCa treatment. This study investigates the role of MAL2 in modulating BCa malignant development and its influence on sunitinib sensitivity.

We aimed to evaluate the relationship between the cumulative area under the concentration-time curve (AUC) for the first and second day of vancomycin (VCM) administration and acute kidney injury (AKI). The primary outcome was the cumulative incidence of AKI. Patients were divided into three groups based on the measured AUC at the first therapeutic drug monitoring (TDM) (800 to less than 1000 µg·h/mL, Low-AUC group; 1000 to less than 1200 µg·h/mL, Moderate-AUC group; ≥1200 µg·h/mL, High-AUC group). Among 180 enrolled patients, 29 (16.1%) developed AKI. In the multivariate Cox proportional hazard analysis, the Moderate- (hazard ratio [HR]: 5.7, 95% confidence interval [CI]: 2.24-14.44) and High- (HR: 11.0, 95% CI: 3.88-31.39) AUC groups were associated with a higher incidence of AKI compared to the Low-AUC group. The accumulation toxicity of VCM was observed, and the cumulative AUC was associated with the development of AKI.

Paclitaxel is the primary chemotherapy agents for many high-incidence cancers, and they also pose a significant risk for peripheral neuropathy. This study investigated the factors influencing paclitaxel-induced peripheral neuropathy (PIPN). We utilized PRO-CTCAE to assess the incidence of PIPN in patients receiving a tri-weekly regimen of single-agent albumin-bound paclitaxel through an online platform within one week after chemotherapy. Multivariable logistic regression was employed to analyze the impact of personal characteristics, clinical data and chemotherapy dose. All the statistical analyses were conducted in R studio. The incidence of acute severe to very severe PIPN was 36.7%, and the risk factors included per 200 mg increment in cumulative dose (OR 1.13, 95% 1.03 ∼ 1.24), estimated glomerular filtration rate < 90 ml/min/1.73m (OR 1.72, 95%CI 1.11 ∼ 2.66), anemia (OR 2.60, 95%CI 1.63 ∼ 4.15), albumin ≥ 40g/L (OR 1.74, 95%CI 1.04 ∼ 2.90), female (OR 1.98, 95%CI 1.19 ∼ 3.29), and overweight (OR 1.74, 95%CI 1.04 ∼ 2.91). The incidence of acute severe to very severe peripheral neuropathy caused by albumin-bound paclitaxel is relatively high. Nutritional status, gender, renal function and cumulative dose were all closely related to this incidence rate. Therefore, in the future, it is of great importance that a comprehensive and systematic assessment regarding the individual risks for patients be carried out in a meticulous manner. Relevant research should be conducted into the mechanisms underlying peripheral neuropathy, with particular attention to the role of individual factors.