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.

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.

Prostate cancer (PCa) is a prevalent malignancy in males with high morbidity and mortality. Although treatment modalities have evolved considerably, tumor resistance, recurrence, and metastasis persist, urgently requiring the exploration of alternative therapies for PCa. There is ongoing research on finding and identifying the use of traditional plant medicine (TPM). Cellular homeostasis comprises a sophisticated network of metabolic processes that functions cooperatively to preserve a stable intracellular environment. Programmed cell death (PCD) plays an important role in PCa mechanism. Thus, they represent an effective strategy for targeting PCa. TPM has been proven to induce PCD through multiple pathways and target in the treatment of PCa. Recent reviews have only focused on the one of the PCD, and autophagy, apoptosis, pyroptosis, ferroptosis, and necroptosis are not simultaneously reviewed.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of gastric cancer; however, they can lead to rare immune-related adverse events (irAEs) affecting the urinary system. Herein, we report a case of non-bacterial cystitis complicated by acute kidney injury (AKI) in a 59-year-old male patient with Alpha-fetoprotein-producing gastric carcinoma (AFP-GC). Following treatment with toripalimab combined with SOX chemotherapy, the patient developed urinary tract irritation symptoms, gross hematuria, and stage II AKI. Cystoscopy revealed diffuse mucosal hemorrhage, and biopsy demonstrated extensive infiltration of CD3+, CD8+, CD4+, and CD20+ lymphocytes, along with high PD-L1 expression and TIA-1 positivity, confirming the diagnosis of non-bacterial cystitis. A full-dose methylprednisolone pulse of 200 mg/day effectively alleviated the symptoms and restored renal function. This case underscores the importance of vigilance for urinary system irAEs in patients receiving ICIs, emphasizing that early identification and systematic evaluation are critical. Full-dose corticosteroids should be used for moderate to severe irAEs. Moreover, this report provides valuable insights into immunotherapy practice and toxicity management in the rare AFP-GC subtype.

The perioperative role of systemic therapy remains poorly defined in borderline resectable or unresectable non-head-and-neck locally advanced cutaneous squamous cell carcinoma (cSCC). We evaluated whether conversion-intent PD-1-based chemoimmunotherapy could restore surgical feasibility in this setting.

Ecteinascidins constitute a family of alkaloid compounds, originally isolated from marine tunicates, that exhibit strong antitumor activity. They act through binding to the DNA minor groove and forming covalent adducts with guanine residues. However, the limited availability of structural data restricts mechanistic insights into their mode of action and hampers the discovery of novel compounds. We report crystal structures of duplex DNA adducts with first-, second-, and third-generation ecteinascidins. The structures show that trabectedin, lurbinectedin, and PM54 bind through their shared A- and B-subunits, forming a covalent bond with the N2 atom of guanine and an extensive network of noncovalent interactions, leading to significant minor groove widening. In contrast, their C-subunit, which differs across the compounds, establishes distinct contacts with the modified strand that affect binding strength and sequence specificity. These structural findings, supported by Förster resonance energy transfer and biochemical assays, reveal the molecular determinants underlying differential sequence selectivity and reactivity. Our results provide a mechanistic framework for the anticancer activity of ecteinascidins and a structural basis to guide the design of next-generation analogues with improved therapeutic potential.

Three-dimensional (3D) cell culture systems provide superior simulation of the tumour microenvironment compared to traditional two-dimensional (2D) cultures. Chemoprevention agent curcumin analog-1.1 (CCA-1.1), a synthetic curcumin derivative, has demonstrated promising anticancer properties against triple-negative breast cancer (TNBC). This study aimed to develop and use a 3D agarose-based culture system for MDA-MB-231 cells to comprehensively evaluate the efficacy of CCA-1.1 as an anticancer agent.

Breast cancer stem cells (BCSCs) are responsible for chemotherapy resistance, metastasis, and tumor recurrence. Paclitaxel-primed mesenchymal stem cells (MSCs) can activate T cells, offering a novel immunotherapeutic approach. However, the molecular mechanisms underlying BCSC-immune interactions remain poorly understood.

Cancer continues to pose a significant worldwide health concern, underscoring the need for the identification of innovative, safer, and more effective therapeutic agents. Phytochemicals obtained from medicinal plants are progressively acknowledged for their anticancer efficacy. This work investigates the antimitotic and antiproliferative properties of the ethanolic extract of Benincasa hispida seeds (EeBHS), known as winter melon, from the Cucurbitaceae family.

Gastric cancer is a major global health concern characterized by high incidence and mortality rates. One of the key challenges in treating gastric cancer is the development of resistance to chemotherapy drugs like cisplatin (DDP). This study aimed to investigate the efficacy of Zuo Jin Wan (ZJW), a traditional Chinese medicine, in overcoming DDP resistance in gastric cancer cells.

With the improving survival rates of malignant tumors, the focus of attention in cancer research is shifting toward a better understanding of long-term treatment-related adverse effects that impact quality of life, with particular focus on cancer-related cognitive impairment. This phenomenon, commonly referred to as "chemobrain" in the literature, manifests as deficits in attention, memory, processing speed, and executive functions. Although the frequency of objectively measured cognitive deficits detected through neuropsychological assessments are moderate, subjective complaints often result in significant deterioration of quality of life. The present review aims to provide a multidisciplinary overview of chemobrain, emphasizing its epidemiological characteristics, neurobiological and psychosocial factors, and options for evidence-based psychological interventions. Alongside neurotoxic, inflammatory, hormonal, and neuroendocrine mechanisms associated with chemotherapy, the review highlights distress, cognitive compensation, and discrepancies between subjective complaints and objectively measurable cognitive deficits. Diagnostic challenges and evidence-based psychotherapeutic approaches-especially cognitive behavioral therapy (CBT), mindfulness-based interventions, and rehabilitation-are also discussed. This analysis highlights the complex nature of chemobrain and the need for further research to develop targeted, individualized therapeutic protocols.