This study aimed to compare changes in postural control in different testing conditions involving sensory disturbances, quality of life and neurotoxicity concerns in women with cancer before and after chemotherapy with taxanes. The second aim was to compare postural control between chemotherapy-induced peripheral neuropathy (CIPN) severity subgroups.

Psoralea bituminosa L. (Fabaceae) is a medicinal plant traditionally used for its antimicrobial, antihyperglycemic, and antioxidant effects. This study investigated its anticancer and antioxidant potential using aqueous and methanol extracts. The methanol extract exhibited higher total phenol (81.57 mg/g) and total flavonoid (39.06 mg/g) contents compared to the aqueous extract. Antioxidant activity, assessed via the DPPH assay, showed moderate potency (IC₅₀: 330.77 µg/mL for aqueous- and 348.27 µg/mL for methanol extracts). Notably, the methanol extract demonstrated significant cytotoxicity against multiple cancer cell lines (IC₅₀: 27.73-53.90 µg/mL) particularly against A549, MDA-MB231, and PC3. Liquid chromatography-mass spectrometry (LC-MS) profiling revealed abundant flavonoids and isoflavones such as daidzein, biochanin A, and 7,3'-dimethoxy-5,6,4' trihydroxyisoflavone in the methanol extract, correlating with its anticancer effects. In contrast, glycosylated flavonoids in the aqueous extract aligned with antioxidant activity. Cheminformatics clustering supported these findings, identifying distinct structural groups with differing drug-likeness scores. Bioinformatics analysis further identified transcriptomic signatures enriched in oxidative phosphorylation and key cancer-related pathways (e.g., TP53, PI3K, NRF2, and MYC), offering mechanistic insight. This integrative approach combining LC-MS, cheminformatics, and bioinformatics provides a cost-effective framework for decoding phytochemical bioactivity and guiding natural product-based drug discovery.

Nanotechnology and information communication technology (ICT) are being combined to develop innovative drug delivery systems for targeted sites, such as tumor cells. The particulate targeted drug delivery (PTDD) system involves drugs containing nanoparticles embedded in nanoscale devices (referred to as bio-nanomachines) that can cross vascular barriers, resulting in an increased concentration of the drug in the targeted cell or tumor. An artificial intelligence bio-cyber interface (AIBCI) operates in both forward and reverse directions, enabling the transfer or control of a desired drug dose without affecting healthy cells, facilitated by the Internet of Biological Nano Things (IoBNT). This paper proposes a multi-compartmental model with an AI bio-cyber interface based on molecular communication technology. The proposed model is formulated as a set of multi-differential equations designed to identify molecular communication-based bio-nanomachines, enabling the quantification of drug concentration at the targeted cell. Unlike conventional compartmental models, the present model is designed to connect both the exterior and interior of the human body. The results suggest that the model has the potential to improve the capacity of target cells to respond to therapeutic drugs while reducing adverse effects on healthy cells. The intra-body nanonetwork proposed in the present study proved superior performance in magnetifying the drug concentrations in diseased cells.

Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

Immune checkpoint inhibitors (ICIs) have transformed the oncology treatment landscape. Despite substantial improvements for some patients, the majority do not benefit from ICIs, indicating a need for predictive biomarkers to better inform treatment decisions.

The somatic mutation theory predicts that cancer risk should scale proportionally with lifetime cell divisions; yet large-bodied and long-lived species exhibit lower-than-expected cancer incidence-a long-standing contradiction termed Peto's paradox. Resolving this paradox and clarifying how tumor mutational burden (TMB) shapes treatment response to immune-checkpoint inhibitor (ICI) therapy remain unmet needs in precision oncology.

Chemoresistance is a main cause of colorectal cancer (CRC) treatment failure. We identified that Bacteroides fragilis is enriched in patients with CRC resistant to chemotherapy in two independent cohorts, and its abundance is associated with poor survival. Consistently, administration of B. fragilis to CRC xenografts and ApcMin/+- and AOM/DSS-induced CRC mice all significantly attenuated the antitumor efficacy of 5-FU and OXA. Mechanistically, B. fragilis colonized colon tumors and mediated its effect via its surface protein SusD/RagB binding to the Notch1 receptor in CRC cells, leading to activation of the Notch1 signaling pathway and the induction of epithelial-to-mesenchymal transition (EMT)/stemness to suppress chemotherapy-induced apoptosis. Either deletion of SusD/RagB or blockade of Notch1 signaling abrogated B. fragilis-mediated chemoresistance. Finally, B. fragilis-targeting phage VA7 selectively suppressed B. fragilis and restored chemosensitivity in preclinical CRC mouse models. Our findings have offered insights into the potential of precise gut microbiota manipulation for the clinical management of CRC.

Ovarian cancer remains the third most prevalent and deadliest gynecologic malignancy worldwide, with most patients eventually developing resistance to platinum-based chemotherapy. This highlights a critical unmet need for innovative multitargeted therapies to address current treatment challenges. In this study, we identified 35 differentially expressed genes (DEGs) through integrated analysis of four GEO ovarian cancer datasets, with validation using TCGA data. Gene Ontology (GO) and KEGG enrichment analyses highlighted key tumor-associated pathways, and protein-protein interaction (PPI) network modeling prioritized CDK1 and TTK as high-value therapeutic targets. We evaluated the association between molecular genomic features and drug responses across the NCI-60 ovarian cancer cell line panel (IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, and SK-OV-3), using a series of salicylanilide-derived compounds and four FDA-approved drugs (cabozantinib, paclitaxel, rapamycin, and niclosamide) from the NCI Developmental Therapeutics Program (DTP). Among these, NSC765690 (MCC22) emerged as the most promising candidate. It demonstrated potent antiproliferative activity, high target selectivity, and strong binding affinity to both CDK1 and TTK. Multi-omics integration, combined with AI-driven network modeling, further elucidated NSC765690's mechanism of action and its relevance to ovarian cancer pathogenesis. Additionally, ADMET and pharmacokinetic profiling confirmed its favorable drug-like properties and low predicted toxicity. Collectively, these findings establish NSC765690 as a potent dual-target inhibitor and exemplify a rational, data-driven drug discovery pipeline for overcoming chemotherapy resistance in ovarian cancer.

Cervical cancer remains one of the leading causes of cancer-related mortality among women worldwide, particularly in low- and middle-income countries, highlighting the need for improved strategies in treatment and management. This study aimed to investigate the anti-cervical cancer potential and molecular mechanisms of Solanecio mannii (S. mannii) aqueous extract using a "multi-compound, multi-target, multi-pathway" approach, integrating both computational and experimental methods. The metabolomics profile of the extract was analysed, and its selective cytotoxicity was assessed against human cervical cancer cell lines (HeLa cells) using the CCK8 assay. A network pharmacology approach identified potential molecular targets and pathways, which was complemented by molecular docking and dynamic simulation. The expression levels of key targets were validated experimentally using quantitative real-time polymerase chain reaction. Additionally, the extract's effects on apoptosis, autophagy, and cell cycle progression were studied experimentally. The aqueous roots extract exhibited selective cytotoxicity against HeLa cells with an IC50 of 12.53 ± 4.983 μg/ml. The network pharmacology analysis identified 25 drug-like compounds targeting 493 unique cervical cancer-associated proteins, forming a protein-protein interaction network of 465 nodes and 2230 edges, and implicated in 178 enriched KEGG pathways. Key targets, including NFΚB1, PIK3CA, HIF1A, STAT3, HSP90AA1, HSP90AB1, PPARG, and ESR1 were experimentally downregulated. Furthermore, S. mannii aqueous roots extract triggered apoptosis through endoplasmic reticulum stress, DNA damage, and activation of the non-transcriptional, P53-mediated mitochondrial apoptotic pathway. Additionally, the extract inhibited hypoxia and autophagy, and induced cell cycle arrest at the G2/M phase, even in the presence of oncogenic HPV proteins (E6 and E7). In conclusion, Solanecio mannii aqueous roots extract demonstrates a "multi-compound, multi-target, multi-pathway" molecular mechanism against cervical cancer.

Antibodies against PD-1 (PD1i), such as cemiplimab and pembrolizumab, have demonstrated significant efficacy in advanced, unresectable cutaneous squamous cell carcinoma (cSCC). These agents elicit durable responses in approximately 45% of patients, contributing to improved aesthetic, functional, and survival outcomes in a subset of individuals with advanced cSCC. This review highlights recent and ongoing research investigating the safety and efficacy of immune checkpoint inhibitors for cSCC in the curative intent perioperative settings, advanced/metastatic setting, and within the immunocompromised patient populations.

The cGAS-STING pathway is a central signalling mechanism in inflammatory responses and can be activated by cisplatin. Increased autophagic activity has been linked to cisplatin resistance in non-small cell lung cancer (NSCLC); however, how autophagy-STING interactions influence the cisplatin response remains unclear. This study investigates how autophagy modulation affects STING expression and cisplatin sensitivity in NSCLC cells with different basal STING levels. Autophagy was inhibited using chloroquine and induced by serum starvation in Calu-1 and H2030 cells. In Calu-1 cells, cisplatin treatment increased STING expression, activated the cGAS-STING pathway, and induced interferon responses correlated with cisplatin concentration. Autophagy inhibition reduced STING expression and interferon activation while enhancing cisplatin sensitivity. Conversely, autophagy induction caused fluctuations in STING expression and decreased cisplatin sensitivity, with ISG15 expression being selectively increased under serum starvation. In contrast, H2030 cells exhibited low basal STING expression and showed minimal responses to cisplatin or autophagy modulation. These findings suggest that STING expression levels critically influence autophagy-mediated responses to DNA-damaging chemotherapy in NSCLC.

Currently, two main challenges in cancer immunotherapy commonly hinder the application of T cell receptor-modified T cell (TCR-T) therapy in the treatment of solid tumors, including the limited ability of T cells to infiltrate solid tumor tissues and the immunosuppressive signals that restrain the anti-tumor efficacy of T cells. In this study, we constructed NY-ESO-1-specific TCR-T and introduced polyethylene glycol-phospholipids (PEG-lipids) to stably modify NY-ESO-1 TCR-T with nonapeptide iRGD, aiming to enhance the penetrability of T cells in vivo, then we combined iRGD-modified NY-ESO-1 TCR-T (iRGD-NY-ESO-1 TCR-T) with PD-1 blockade to alleviate immunosuppressive signals. In result, it is suggested that stably modifying NY-ESO-1 TCR-T with iRGD is a simple and effective strategy to enable TCR-T to target and penetrate solid tumor tissues. Besides, the combination of iRGD-NY-ESO-1 TCR-T with PD-1 blockade presents a novel synergistic strategy for the treatment of refractory NY-ESO-1-positive solid tumors.

Local-regional therapy combined with immune checkpoint inhibitors (ICIs) and lenvatinib has shown promising anti-tumor activity in advanced biliary tract cancer. However, the efficacy and safety of integrating local-regional therapy with chemotherapy, ICIs, and lenvatinib in advanced intrahepatic cholangiocarcinoma (ICC) remain unclear. This study evaluated the efficacy and safety of first-line treatment combining local-regional therapy, chemotherapy, ICIs, and lenvatinib in advanced ICC.

Bioinspired nano/micromotors with drug delivery capabilities are emerging tools with the promising potential to treat numerous diseases. However, some major challenges must be overcome before reaching real biomedical applications. Above all, it is necessary to design engines that employ biocompatible and bioavailable fuels to induce efficient propulsion in biological environments. In addition, ideal nanomotors should also be capable of delivering the cargo on-command using selected stimuli. To tackle these challenges, we herein present the design and evaluation (both in vitro and in vivo) of a glucose-driven gated Janus nanomotor that performs on-demand anticancer drug delivery to treat solid tumors. The motor's nanoarchitectonics is based on the anisotropic conjunction of catalytic platinum nanodendrites (PtNds) and a mesoporous silica nanoparticle (acting as a nanocontainer for anticancer drug doxorubicin) capped with enzyme glucose oxidase (GOx). Autonomous nanomotor movement is achieved thanks to two catalytic components, GOx and PtNds, in a hybrid cascade reaction: GOx transforms glucose to give H2O2 that is subsequently catalyzed by PtNds into H2O and O2. Besides, gatekeeper moieties (GOx) respond to the presence of intracellular proteases, which induces doxorubicin delivery. Biological experiments with the nanomotor are carried out in cancer cell cultures, three-dimensional (3D) tumor models (spheroids), in vivo and in patient-derived organoids (PDOs). A strong anticancer effect is found and attributed to the synergistic combination glucose-induced propulsion, controlled drug delivery, elimination of glucose (by GOx), ROS production (H2O2 generation by GOx) and hypoxia reduction (O2 generated by PtNds). Taken together, this study advances the engineering of endogenously fueled nanomotors for in vivo operation and provides insights into the application of active particles in cancer therapy toward clinical application.

Tryptophan (Trp) metabolism is a complex and important biochemical process in humans. It is vital in protein synthesis and is a precursor of various bioactive molecules. Trp is metabolized through the kynurenine, serotonin and indole pathways, mediating diverse physiological functions, including neurotransmitter synthesis, immune regulation, antioxidant effects, and biosynthesis of niacin and melatonin. These metabolic pathways maintain essential functions under normal physiological conditions. However, they are significantly affected by various types of cancers. Trp metabolites regulate tumor angiogenesis, affect the self‑renewal of cancer stem cells, and participate in immune evasion and cell death through complex mechanisms. As the mechanisms underlying Trp metabolism in diseases are increasingly being elucidated, targeting Trp metabolic pathways has emerged as a promising therapeutic strategy. Further investigation of the molecular mechanisms underlying Trp metabolism and its role in diseases may provide new perspectives and approaches for diagnosing and treating diseases.

Diseases such as cancer, neurodegenerative and cardiovascular disorders, and diabetes are becoming more and more common, raising global concerns about prevention and treatment. An abnormality in cell growth can lead to the formation of tumors or neoplasms. Cancer is a global public health problem and always requires further advances in the field due to the obstacles that arise during treatment.

Quercetin, a prevalent flavonol compound, has gained attention for its multifaceted mechanisms of action against various cancers, highlighting its potential as an adjunctive therapy in cancer treatments. This review aims to systematically evaluate the structural optimization, mechanisms of action, and clinical applications of quercetin and its nano-derivatives in cancer treatment. Employing a bibliometric analysis of 6231 articles from the Web of Science Core Collection, we observed a notable increase in annual publications, particularly from the USA and China, indicating a growing interest in quercetin's therapeutic potential. Our findings reveal that quercetin enhances the efficacy of conventional therapies by modulating critical signaling pathways, thereby increasing cancer cell sensitivity while simultaneously protecting normal tissues from therapy-induced damage. Structural modifications, including glycosylation, methylation, sulfation, and glucuronidation, alongside nanoparticle formulation, significantly improve the stability, solubility, and bioavailability of quercetin, enabling targeted drug delivery. Despite the promising preclinical outcomes, the clinical translation of quercetin remains nascent, necessitating further rigorous research to validate its safety and efficacy in human subjects. In conclusion, while quercetin exhibits substantial anticancer properties and therapeutic potential, future studies should focus on expanding sample sizes, elucidating metabolic pathways, and conducting comprehensive clinical trials to inform its application in oncology.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Moringa oleifera and Plukenetia volubilis (Sacha inchi) have been reported to enhance various biological functions, including antitumor and antiproliferative activity.

Background: Although presurgical endocrine therapy has been used to enhance the rate of breast cancer conservation, its prognostic relevance is unknown. The search for a valid prognostic factor equivalent to pathological complete response in presurgical chemotherapy remains a challenge in presurgical endocrine therapy. This study investigated the efficacy of presurgical short-term endocrine therapy (preSTE) and assessed prognostic factors, including the preoperative endocrine prognostic index (PEPI) score. Methods: From October 2012 to November 2021, 269 postmenopausal women diagnosed with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative breast cancer underwent endocrine therapy with a nonsteroidal aromatase inhibitor during the presurgical waiting period. The primary endpoint was to assess the changes in tumor size using ultrasonography, and Ki67 expression levels before and after preSTE. The secondary endpoint was the prognosis of patients categorized using the PEPI score. Results: The median age of patients was 68 years (range, 41-89 years). The median tumor size was 1.65 cm (range, 0.4-7.5 cm). The average pretreatment Ki67 expression level was 10% (range, 0%-90%). The median duration of endocrine therapy was 39 days (range, 2-88 days). Tumor diameter and Ki67 expression levels were significantly decreased to 1.43 cm (range, 0.45-5.83 cm) and 3.0% (range, 0%-85%) after preSTE, respectively. After the median observation period of 928 days, patients with PEPI scores ≥ 4 showed worse disease-free survival compared with those with lower PEPI scores. In terms of mortality, patients with PEPI score ≥ 4 had worse overall survival than did patients with lower PEPI scores. Conclusions: Endocrine therapy during the waiting period for surgery might be effective in reducing tumor size, and the Ki67 expression level and PEPI score might be useful in predicting the prognosis of patients with postmenopausal HR+ breast cancer.

To investigate the comprehensive landscape of hepatotoxic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs), with a special focus on evaluating the potential risk of lethal hepatotoxic AEs.