The optimal choice between sedating histamine H1 antagonists (sAHs) and non-sedating histamine H1 antagonists (nsAHs) for preventing infusion-related reactions (IRRs) during daratumumab subcutaneous (DARA-SC) therapy remains unclear. Here, we aimed to compare the efficacy and safety of nsAH and sAH as premedication for DARA-SC therapy. Patients with multiple myeloma or light-chain amyloidosis who received DARA-SC therapy at eight hospitals were enrolled in this prospective, multicenter, observational study. Patients were categorized into nsAH and sAH groups based on their premedication. IRRs and drowsiness were assessed using patient-reported questionnaires, including the Stanford Sleepiness Scale (SSS) and the Japanese Epworth Sleepiness Scale (JESS), at baseline, post-administration (Q2), and before bedtime (Q3). Overall, 104 patients (nsAH, n = 49; sAH, n = 55) were analyzed. No significant differences were observed in the IRR incidence between the nsAH and sAH groups at Q2 (8.2 vs. 9.1%) or Q3 (13 vs. 17%). Conversely, the incidence of new-onset drowsiness at Q2 was significantly lower in the nsAH group (13%) than in the sAH group (32%, p < 0.05). Additionally, the increase in SSS from baseline to Q2 was significantly lower in the nsAH group than in the sAH group (p < 0.05). No significant differences were observed in JESS scores. Thus, nsAH was associated with reduced early post-administration drowsiness and there were no statistically significant differences in IRR preventive effects compared to that for sAH, suggesting that nsAH may reduce sedation without a significant increase in the incidence of IRRs; however, these hypothesis-generating findings warrant verification through future prospective comparative trials.

Given the limited Japanese real-world evidence, this study aimed to evaluate the survival and safety of adjuvant nivolumab after neoadjuvant chemotherapy in patients with an incomplete pathological response to esophageal squamous cell carcinoma (ESCC).

Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.

Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2-proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.

Pediatric osteosarcoma is a rare and aggressive malignancy with limited treatment options in cases of progression or metastasis. Regorafenib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and other kinases, currently approved in Japan for certain gastrointestinal cancers. Its clinical use in osteosarcoma, especially in pediatric patients, has not been well established.

Flavones are naturally occurring compounds with a wide range of biological activities and therefore they represent a privileged scaffold in medicinal chemistry. We recently reported the systematic synthesis of 3-styrylflavones possessing variously hydroxylated D-ring moieties, which indicated significant antiproliferative activity. To determine how the bioisosteric replacement, such as the replacement of a hydroxyl group by an amino/nitro group, influences antiproliferative activity, we designed and synthesized a series of 3-styrylflavones possessing variously nitrogenated D-ring moieties.

Matrix metalloproteinases (MMPs) are important enzymes in extracellular matrix degradation. Several cancer types overexpress MMPs, indicating that MMP inhibition may be a viable approach to induce antitumor activity. To explore this, we designed UTX-121, a molecule in which the sulfonamide group of celecoxib is replaced with a methyl ester group. From this structure, a range of UTX-121 derivatives were developed in which the tolyl moiety was modified. The MMP inhibitory effects of these derivatives were then examined.

Dihydroaustrasulfone alcohol (DA), a synthetic precursor of austrasulfone derived from the soft coral Cladiella australis, has demonstrated cytotoxic activity against various cancer types. However, its antitumor effects and underlying mechanisms in human leukemia cells remain unknown. This study aimed to investigate the anticancer effects of DA in leukemia cell models and to elucidate its mechanisms of action.

This study aimed to investigate the effects of cephaeline on oral squamous cell carcinoma (OSCC) cell lines, with a focus on cancer stem cell (CSC) regulation and its interaction with cisplatin.

Chemotherapy-induced peripheral neuropathy (CIPN) is frequent, having a lasting impact on the quality of life and is neither preventive nor do causal treatment options exist. The aim of this study was to systematically evaluate an in vivo female SKH-1 mouse model with respect to the temporal occurrence of paclitaxel-induced peripheral neurological dysfunction.

Taxane-induced peripheral neuropathy (TIPN) is a common side effect of chemotherapy that significantly impacts patients' quality of life. This study evaluated the efficacy of professional acupuncture and self-care using press-tack needles for TIPN.

Epithelioid angiomyolipoma (E-AML) is a rare renal tumor, which can exhibit malignant potential. Because angiomyolipomas frequently harbor TSC1/TSC2 alterations, mTOR inhibitors are commonly used. However, durable disease control remains inconsistent. The potential for long-lasting response with immune checkpoint inhibitors supports exploring their role in E-AML. We report a patient with highly symptomatic, locally advanced renal E-AML treated with first-line ipilimumab plus nivolumab. The patient experienced rapid symptomatic and radiographic improvement after treatment initiation. She subsequently developed immune-related sarcoidosis, which resolved after discontinuation of immunotherapy and with corticosteroids. Given sustained disease control, she underwent delayed nephrectomy demonstrating complete pathologic response in the primary tumor. Genomic analysis revealed a germline mutation in FLCN consistent with Birt-Hogg-Dubé syndrome. T-cell receptor sequencing identified a shared expanded T-cell clone in peripheral blood and within the tumor. With extended follow-up for over 5 years, she remains in durable remission after dual immune checkpoint blockade. To our knowledge, this is the first report of dual immune checkpoint blockade in renal E-AML. This case demonstrates that first-line ipilimumab plus nivolumab can induce deep, durable response-including complete pathologic response-in a rare malignancy with limited standard treatment options, supporting further evaluation of immunotherapy in this disease.

The extracellular cyclic GMP-AMP (cGAMP)-ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) axis is an emerging pharmacological target that links tumor-intrinsic DNA stress to antitumor immunity. Tumor cells can generate cGAMP in response to chromosomal instability, micronuclear rupture, replication stress, and therapy-induced DNA damage. After export into the tumor microenvironment, extracellular cGAMP may be transferred to antigen-presenting cells and activate stimulator of interferon genes (STING)-dependent type I interferon and C-X-C motif chemokine ligand 10 (CXCL10) programs, thereby supporting dendritic-cell activation, immune priming, and cytotoxic T-cell recruitment. ENPP1 restricts this process by degrading extracellular cGAMP and by contributing to nucleotide catabolism associated with AMP- and adenosine-dependent immunosuppression. Accordingly, pharmacological ENPP1 inhibition differs from direct STING agonism by preserving endogenous tumor-derived cGAMP rather than imposing exogenous receptor activation. This Review summarizes the mechanistic basis, pharmacological rationale, and translational challenges of targeting the extracellular cGAMP-ENPP1 axis in cancer. We discuss ENPP1 inhibitors and cGAMP-stabilizing approaches, focusing on mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) relationships, target engagement, therapeutic window, and potential immunotoxicological constraints. We also propose a biomarker-guided framework incorporating cGAMP-generating capacity, ENPP1 expression and enzymatic activity, STING-response competence, and on-treatment pharmacodynamic conversion. Finally, we evaluate rational combinations with radiotherapy, chemotherapy, DNA damage response-targeted agents, immune checkpoint blockade, and immune-metabolic modulators. Clinical translation will require patient stratification, schedule-aware combination design, and robust pharmacodynamic validation in early-phase studies.

Antibiotics compromise the efficacy of immune checkpoint inhibition (ICI) therapy in cancer, but the underlying mechanism remains unclear. In this issue of Cancer Cell, Mallard de La Varende et al. identify dysbiosis-associated tauro-conjugated bile acids as drivers of ICI non-response and γ-glutamyl transferase (γGT) as a predictive biomarker.

Bortezomib is a proteasome inhibitor used to treat cancers such as Multiple Myeloma and Mantle Cell Lymphoma. Due to its narrow therapeutic index, accurate quantification in biological matrices is essential for monitoring drug exposure, optimizing dosing, and assessing tissue distribution. The aim of this study was to develop and validate LC-MS/MS methods for the quantification of bortezomib in rat serum and rat sciatic nervous tissue. A rapid serum assay based on one-step protein precipitation and a nervous tissue assay were established using 2H8-Bortezomib as an isotope labeled internal standard. Calibration ranges were 0.920-100 ng/mL for serum and 4.00-100 ng/g for nervous tissue. Bortezomib and its internal standard were detected using high-resolution MRM in positive-mode electrospray ionization, with a total acquisition time of 4 min per run. The serum method was validated according to ICH M10 guideline, ensuring compliance with parameters including accuracy, precision, matrix effects, recovery, stability, selectivity, reinjection reproducibility, and carry-over. The nervous tissue method underwent partial validation, assessing key parameters to ensure reliable quantification. The application of these methods to authentic rat samples demonstrated their suitability. The developed assays provide rapid and sensitive quantification of bortezomib in serum and sciatic nervous tissue. The simple sample preparation procedures and short run times support their use in pharmacokinetic and tissue distribution studies.

This study explored the potential association between paclitaxel (PTX) and macular oedema (ME), a rare adverse event, through pharmacovigilance analysis using a large-scale spontaneous reporting database.

Autophagy is a lysosome-dependent recycling process that maintains cellular homeostasis and helps cells adapt to therapeutic stress. In oral squamous cell carcinoma (OSCC), dysregulated autophagy may promote chemoresistance by supporting metabolic adaptation, removing damaged cellular components, and limiting treatment-induced cell death. Its effects are nevertheless context dependent, as autophagy can also interact with apoptosis, ferroptosis, and other cytotoxic pathways. This review summarizes molecular mechanisms linking autophagy to OSCC chemoresistance, focusing on non-coding RNAs, p53/TP53, BECN1, ATG-related proteins, oncogenic signaling networks, and emerging biomolecular-condensate mechanisms. It also evaluates therapeutic strategies, including early- and late-stage autophagy inhibition, mTOR-targeted modulation, metabolic interventions, genetic approaches for mechanistic validation, ferroptosis-autophagy combinations, and nanotechnology-assisted delivery systems. Although promising effects have been reported in cell lines, drug-resistant derivatives, cancer stem cell-like populations, and xenograft models, OSCC-specific clinical evidence remains limited. Future progress will require rigorous assessment of autophagic flux, careful interpretation of related head and neck squamous cell carcinoma evidence, biomarker-guided patient stratification, and validation in clinically relevant models. Integrating autophagy biology with molecular stratification and rational combination therapy may help overcome chemoresistance in OSCC.

Chemotherapy/immune checkpoint inhibitor (ICI) therapy is increasingly standard of care for a range of cancers. Increasing numbers of emergency cancer presentations mean alternative pathways are required to ensure sustainable services and improve outcomes. Febrile neutropenia (FN) is common in patients treated with chemotherapy/ICI therapy. Risk stratifying patients with FN is essential to personalise acute management and optimise use of healthcare resources. Management of patients with low-risk FN in an outpatient setting is proven to be safe and effective. The MASCC score is well validated for risk stratification in FN, and patients with a score ≥ 21 are likely to be suitable for outpatient management. It has not been validated in patients treated with combined chemotherapy/ICI regimens. This MASCC position paper outlines an approach for acute ambulatory management of low-risk FN in this cohort and produces ten position points. A literature search was performed up to the 31st May 2025 for outpatient management of FN in patients treated with chemotherapy/ICI therapy. Only one paper met the criteria highlighting the need for prospective and real-world data. Patients treated with a MASCC score < 21 are high risk and require standard neutropenic sepsis management. Empirical usage of high-dose steroids in patients presenting with FN on chemo/ICI therapy with grade ≥ 3 diarrhoea and/or transaminitis is not recommended. Patients treated with chemotherapy/ICI therapy with low-risk FN should be treated on the same pathway as those treated with chemotherapy alone with inclusion criteria adapted to recognise their eligibility. ICI-mediated neutropenia should be considered in patients receiving combined chemotherapy/ICI therapy when the timing of presentation is unanticipated or there is a failure of neutrophil recovery with persistent grade 3/4 neutropenia 10 days following administration. Initial treatment of suspected ICI-mediated neutropenia is to commence high-dose steroids and consider short-acting G-CSF.

Triple-negative breast cancer (TNBC) primarily relies on traditional adjuvant chemotherapy and radiotherapy, which have significant side effects and are prone to drug resistance. Poly ADP-ribose polymerase inhibitor (PARPi) has been approved for TNBC patients with BRCA mutation, but some BRCA wild-type patients with homologous recombination deficiencies are also sensitive to PARPi. Therefore, it is important to identify potential molecules that influence PARPi sensitivity in BRCA wild-type TNBC and to explore their specific mechanisms. Through CRISPR-cas9 loss-of-function screening, the lncRNA MTUS2-AS1 was identified to be significantly correlated with PARPi sensitivity in BRCA wild-type TNBC cells. In vitro and in vivo experiments were performed to investigate its function and underlying mechanism. We found that MTUS2-AS1 knockdown suppressed DNA damage repair and enhanced the anticancer effects of PARPi in BRCA-wild TNBC cells. Mechanistically, MTUS2-AS1 upregulates DDX5 protein expression by maintaining its stability, thereby promoting R-loop resolution, and suppressing DNA damage. Knocking down MTUS2-AS1 accelerated DDX5 protein degradation, reduced DDX5 protein expression, inhibitd R-loop resolution, promoted DNA damage, and ultimately enhanced the PARPi sensitivity in TNBC cells. Our study provided new insights into exploring the key molecules and mechanisms influencing the sensitivity of PARPi treatment and had great significance for screening benefit population and expanding the indications of PARPi treatment.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet clinical responses remain highly variable, and microbiome-associated findings lack reproducibility across studies. Increasing evidence implicates the gut microbiome in modulating ICI efficacy; however, findings remain inconsistent at the taxonomic level, raising the possibility that functionally convergent immunological mechanisms may underlie this apparent variability. To address this, a critical synthesis was conducted, integrating bibliometric mapping of publications indexed in the Web of Science Core Collection (2013-2025; n = 2,195) with a secondary analysis of ClinicalTrials.gov to evaluate interventional activity. Bibliometric approaches assessed scientific production, thematic evolution, and co-citation structure, complemented by a cross-cohort functional integration of representative clinical and preclinical studies to evaluate whether microbiome-ICI interactions converge on shared immunological pathways despite divergent taxonomic signatures. Publication output increased steadily, with a marked translational surge following landmark clinical studies in 2018 and a peak in trial initiation in 2021. Thematic analyses revealed a shift from mechanistic and tumor-centered research toward clinically oriented and intervention-driven themes, including microbiome modulation, microbial metabolites, and the tumor microenvironment. Although individual response-associated taxa differed substantially across independent cohorts, qualitative functional integration supported a model of convergence in immunomodulatory pathways involving short-chain fatty acid production, dendritic cell activation, and CD8+ T-cell priming. Collectively, these findings suggest that apparent taxonomic inconsistencies across microbiome-ICI studies may reflect underlying functional convergence rather than biological contradiction, supporting a shift toward function-based frameworks for biomarker discovery and microbiome-directed immunomodulation.