Multimodal tumor therapy based on "all-in-one" nanoplatforms enhances therapeutic efficacy, simplifies the construction process, and improves material utilization. Elemental selenium was successfully supported on upconversion nanoparticles (UCNPs) to constitute the near-infrared (NIR) light-responsive UCNP@Se heterostructures for the first time. Under 980 nm irradiation, the UCNP@Se heterostructures could not only produce holes and superoxide radicals •O2- but also catalyze the generation of hydroxyl radicals •OH by highly elevated levels of H2O2 in tumor cells to kill the tumor cells. In addition to the superior photocatalytic performance, elemental selenium itself also exhibited inherent inhibition activity against tumor cells. On the basis of the binding of anthracycline anticancer drugs such as doxorubicin (DOX) to the supported elemental selenium through Cu2+ bridging coordination, the UCNP@Se-Cu-DOX drug delivery system was constructed. The introduction of Cu2+ not only improved the efficient loading of DOX but also achieved the "AND" logic-controlled release of DOX under the combined stimuli of low pH and overexpressed glutathione (GSH) in tumor cells. Moreover, the loaded Cu2+ reacted with the overexpressed GSH to generate the active species CuII-GSSG upon NIR light irradiation, which further promoted tumor cell apoptosis. The NIR light-responsive UCNP@Se-Cu-DOX drug delivery system achieved the combination tumor therapy of selenium therapy, photocatalytic therapy, and logic-gated chemotherapy and has great potential applications in tumor therapy.

This study evaluated the effectiveness of a mobile application in tracking symptoms and improving symptom management and quality of life (QoL) among breast cancer patients undergoing chemotherapy in Thailand.

Temozolomide (TMZ), which is an alkylating agent, is the standard chemotherapeutic drug used for glioma treatment. However, the development of resistance to TMZ limits its efficacy. Thus, identifying novel therapeutic targets is necessary.

Tremendous efforts have been devoted to developing chemodynamic cancer therapy (CDT) platforms targeting intracellular antioxidant defense systems to realize an enhanced efficacy. However, such a strategy can be severely limited by the activation of compensatory antioxidant defense mechanisms in cancer cells. Herein, we present the rational design of a nanozyme-based CDT platform that can perturb compensatory antioxidant mechanisms in cancer cells for improved therapeutic efficacy. In the formulation, the metal-organic framework-based disruptor with peroxidase-mimicking activity can not only catalyze the conversion of the intracellular hydrogen peroxide into highly cytotoxic hydroxyl radicals for cancer cell killing but also disrupt the intracellular glutathione peroxidase 4-dihydroorotate dehydrogenase compensatory antioxidant system to provide significantly reinforced CDT efficacy. The present study sheds light on improving the outcomes of therapeutics that rely on the induction of oxidative stress by integrating the ability to disrupt intracellular compensatory antioxidant defense mechanisms into nanomedicine design.

Protein arginine methyltransferase 5 (PRMT5) is an epigenetic-related enzyme that has been shown to be a promising target for the treatment of human cancers. In prostate cancer, gene knockout has been shown to inhibit cancer cells by regulating the androgen receptor (AR), but this method has no effect on advanced prostate cancer without AR expression, and existing anticancer drugs are effective only in the current stage and promote the progression of cancer to advanced prostate cancer. We hope to design and synthesize a new compound that can inhibit prostate cancer at different stages. A series of candidate PRMT5 inhibitor molecules were designed on the basis of virtual molecular docking screening, and the binding mode was predicted via molecular docking simulation. Prostate cancer cell proliferation was detected by CCK-8, EdU, and flow assays, which verified the changes in the cancer cell cycle. Migration and invasion assays verified the effects of the compounds on the metastatic function of prostate cancer cells. Finally, Western blotting was used to detect the mechanism of action of the compounds in the treatment of prostate cancer. In prostate cancer, gene knockout has been shown to inhibit cancer cells by regulating the AR, but it has no effect on advanced prostate cancer without AR expression, and existing anticancer drugs are effective only in the current stage and promote the progression of cancer to advanced prostate cancer. SJL2-1 may be a promising compound for novel therapies for early androgen-sensitive prostate cancer and advanced castration-resistant prostate cancer (CRPC).

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective autophagy, an immunosuppressive tumor microenvironment (TME), altered signaling pathways, and active drug efflux transporters. Recent advancements to overcome these resistance mechanisms, including enhancing TMZ bioavailability through nanoparticle-based delivery systems and the inhibition of efflux transporters, have been explored. Novel therapeutic approaches that target DNA repair pathways and manipulate autophagy are highlighted. Immunotherapeutic interventions reversing immune suppression and metabolic strategies targeting tumor metabolism offer additional avenues. Emerging therapies such as CRISPR-based gene editing, phytochemical combinations, repurposed drugs, and novel TMZ analogs designed to bypass MGMT-mediated resistance are also discussed. This review highlights current developments and identifies emerging areas, with the goals of enhancing clinical outcomes and prolonging survival for glioma patients.

This review aimed to evaluate the effects of exercise-based interventions on cancer therapy-related cardiovascular toxicity (CTR-CVT) in individuals with cancer.

Febrile neutropenia (FN) is a life-threatening complication of chemotherapy. Although practice guidelines suggest the use of existing prediction models when making decisions to prevent and treat FN, recent evidence suggests that these models are limited in their discriminative ability. This study aims to systematically review and critically evaluate the recent literature to assess the question: what evidence-based clinical prediction models can be used to predict FN or its outcomes?

Aberrant expression of histone deacetylases (HDACs) is associated with cancer drug resistance and tumor progression. While considerable studies and effort have been devoted to developing novel HDAC inhibitors in cancer therapy, hydroxamate-based HDAC inhibitors have gained growing interest for their broad-spectrum anti-tumor properties. We developed a series of HDAC inhibitors featuring a hydroxamate moiety, and WMJ-J-09 was selected due to its potent cytotoxic effect in colorectal cancer (CRC) cells, and its molecular mechanisms driving CRC cell death were characterized. WMJ-J-09 reduced cell viability, arrested the cell cycle at the G2/M phase, and triggered apoptosis. Mechanistically, it activated LKB1-p38MAPK signaling, leading to p53 phosphorylation and acetylation, which elevated p21 and suppressed survivin levels. WMJ-J-09 also acetylated α-tubulin, impaired microtubule assembly, and acetylated survivin, resulting in proteasomal degradation. Both LKB1 siRNA and anacardic acid, a histone acetyltransferase inhibitor, reversed WMJ-J-09-reduced survivin, confirming its dual effects on survivin at transcriptional and post-translational levels. In vivo, the subcutaneous growth of HCT116 CRC xenografts was reduced by WMJ-J-09. In conclusion, WMJ-J-09 causes CRC cell death via the LKB1-p53-survivin signaling pathway and HDAC inhibition, leading to acetylation of α-tubulin, p53, and survivin. This study highlights WMJ-J-09's potential as a promising therapeutic candidate for CRC treatment.

Human topoisomerase II (topoII) is a well-known and validated target for cancer treatment. We previously reported a first set of 6-amino-tetrahydroquinazoline derivatives as novel human topoII inhibitors. Here, we report on the expansion and this molecular scaffold and present 17 additional analogs centered on the tetrahydropyrido[4,3-d]pyrimidine heterocycle. Some of these compounds exhibit promising topoII inhibitory and antiproliferative activities. Compound 24 (ARN21929) shows good in vitro potency, with an IC50 of 4.5 ± 1.0 µM, excellent kinetic and thermodynamic solubility, and good metabolic stability. Our results indicate that this new chemical class of topoII inhibitors deserves further exploration and represents a promising starting point for developing novel and potentially safer topoII-targeted anticancer drugs.

ICRF193 is a catalytic inhibitor of Topoisomerase 2 (TOP2), one of the major targets in cancer therapy. Although ICRF193 has not been approved for clinical use, it has potential implications in chemotherapy. In this study, we aimed to investigate the use of ICRF193 in chemotherapy in co-treatment with other drugs. To identify compounds that have synergistic effects with ICRF193, we optimized a cytotoxicity assay with combinations of ICRF193 in a 1536-well plate format and screened 2678 compounds, including clinically approved and investigational drugs, for their cytotoxicity in the presence and absence of ICRF193. From the screening and confirmation assays, etoposide, a known TOP2-targeting drug, was found to have a synergistic effect with 200 nM ICRF193 across multiple cancer cell lines, including HCT116, MCF7, and T47D. On the other hand, ICRF193 suppressed the toxicity of etoposide at higher concentrations (> 10 µM). In the follow-up studies, we found that ICRF193 and etoposide synergistically induced DNA double-strand breaks and subsequent G2 phase accumulation. Interestingly, this synergistic effect was observed only with etoposide and not with other TOP2 inhibitors in the tested compound library. Taken together, our results indicate that ICRF193 has a specific functional interaction with etoposide that enhances its genotoxic potential.

The patient was a 54-year-old woman with chronic myeloid leukemia. Ten months after treatment with dasatinib, she developed a cough. Imaging studies showed ground-glass patterns in the lower lung fields of both lungs, which led to suspicion of drug-induced lung injury and prompted discontinuation of dasatinib. A transbronchial lung biopsy showed epithelioid granuloma without necrosis in the alveolar region. There were no other systemic symptoms or signs to support a diagnosis of sarcoidosis. Fifteen days after withdrawal of dasatinib, both the cough and X-ray findings improved. Granulomatous tissue was detected on lung biopsy, which indicates that drug-induced sarcoidosis-like reaction (DISR) may cause interstitial lung injury as a respiratory complication of dasatinib treatment. Case reports of DISR following administration of immune checkpoint inhibitors and immunomodulatory drugs have recently become more frequent. Here we report a case of dasatinib-induced DISR with a review of the literature.

The purpose of this work was to use molecular docking techniques to examine the chemical makeup and biological activity of the petroleum ether and chloroform extracts (SPEE and CHSE, respectively) of Coffee arabica seeds. According to the GC/MS results of SPEE, the extract contains 28 components, which account for approximately 96% of the total. These substances fall under several categories of phytoconstituents. Nevertheless, the extract contains 28 compounds, which make up 99.1% of the total, according to the CHSE GC/MS data. Alcohols (4.93%) with 2-ethyl-1-hexanol as the primary compound, monoterpenes (3.95%) with 4-ethyl-1-octyn-3-ol accounting for 2.92%, aromatics (2.67%), esters (38.31%) with methyl palmitate as the primary (16.71%), caffeine (28.81%), hydrocarbons (10.85%) with 7-octadecene as the primary compound, and ketones (5.13%) with 2-ethyl-1-cyclohexanone as the primary (3.04%) are among them. Only Bacillus subtilis was susceptible to the modest antibacterial activity of both extracts. Whereas CHSE successfully targeted breast (IC50 = 146.10 μg/mL) and colon cancer cells (IC50 = 111.90 μg/mL), SPEE showed strong cytotoxicity against hepatocellular carcinoma (IC50 = 42.41 μg/mL) and breast cancer cells (IC50 = 57.76 μg/mL) in anticancer studies.

Diabetic retinopathy (DR) remains a leading global cause of blindness, significantly affecting the quality of life of patients with diabetes. This clinical observational study was designed to comprehensively assess the synergistic effects of anti-vascular endothelial growth factor (anti-VEGF) drugs and panretinal photocoagulation (PRP) on the progression of DR and visual outcomes. A total of 120 patients with severe non-proliferative or proliferative DR were prospectively recruited and randomly assigned into two groups: the combination therapy group (anti-VEGF + PRP) and the PRP monotherapy group. The results clearly demonstrated that the combination group achieved remarkable anatomical and functional improvements, with a more substantial reduction in macular edema and neovascularization. Long-term follow-up over 24 months further revealed better visual acuity retention and a lower incidence of complications in the combination group. These findings strongly support the integration of anti-VEGF agents into traditional PRP protocols for the effective management of advanced DR.

Hepatocellular Carcinoma (HCC) is a widely recognized aggressive tumor, owing primarily to its high recurrence and metastasis risk. On the other hand, Ailanthone (AIL), a natural plant derivative, has demonstrated diverse pharmacological properties and a capacity to induce cell death among other mechanisms. Consequently, it could be employed to suppress HCC proliferation. Nonetheless, AIL's precise targets and mechanisms of action in inhibiting HCC cell growth remain unclear, forming the basis of this study.

DPYD-guided dosing enhances safety of fluoropyrimidine-based chemotherapy. However, approximately 23 % of patients still experience severe toxicity unexplained by the four commonly tested DPYD-variant alleles. Elevated pre-treatment uracil levels have been proposed as a surrogate marker for reduced DPD activity and an independent predictor of toxicity. This prospective study evaluated whether uracil-guided dose individualisation can reduce severe fluoropyrimidine-induced toxicity in DPYD wild-type patients.

Zolbetuximab, a first-in-class monoclonal antibody targeting Claudin 18.2 (CLDN 18.2), has demonstrated significant survival benefit when combined with chemotherapy in HER2-negative, CLDN 18.2-positive advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. However, its integration into clinical practice presents two major challenges: the best treatment selection between zolbetuximab or immune checkpoint inhibitor (ICI)-based regimens in patients co-expressing programmed death-ligand 1 (PD-L1), and the management of zolbetuximab-related nausea and vomiting (N/V). We critically reviewed evidence from randomized controlled trials, regulatory approvals, and recent expert consensus on zolbetuximab management. In CLDN 18.2-positive/PD-L1-positive patients, ICIs may offer greater long-term survival benefit especially in case of high PD-L1 CPS, while zolbetuximab may be preferred in patients with negative-to-low CPS or ICIs contraindications. N/V, reported in more than three-quarter of patients, is more frequent and severe during the first infusion, due to zolbetuximab loading dose and faster infusion rate. Proper management includes accurate adherence to high-risk antiemetic protocols (including NK-1/5-HT3 antagonists and corticosteroids) and careful control of infusion rates with a stop and go strategy. In case of CLDN 18.2 and PD-L1 CPS co-positivity, we advocate the use of PD-L1 CPS ≥ 10 as a practical decision-making threshold for favoring ICI-based regimens. However, the treatment selection should be tailored on comorbidities, comprehensive molecular characterization and available subsequent options. To ensure the optimal use of zolbetuximab, special attention is required during the first cycle, due to higher risk of infusion-related N/V. We suggest that the optimization of both prophylactic and on-treatment antiemetic strategies is essential to enhance zolbetuximab adherence and maximize clinical outcomes.

The unique characteristics of cancer are crucial for comprehending the processes underlying cancer initiation, development, and maintenance. These hallmarks guide the development of novel therapeutic strategies aimed at fundamental traits of cancer, resulting in more targeted therapies with the possibility for sustained effectiveness and minimized adverse effects. Drug repurposing, a novel approach that leverages the known safety and pharmacological properties of existing drugs, has surfaced as a viable alternative to traditional drug development. This method expedites the timescale for introducing novel medicines into clinical practice, often demonstrating reduced failure rates in clinical trials. Recent data substantiates the therapeutic efficacy of many repurposed medications in the management of oral squamous cell carcinomas (OSCC), a highly aggressive and treatment-resistant malignancy. Prominent instances include metformin, phenformin, propranolol, acetylsalicylic acid, celecoxib, itraconazole, statins, dihydroartemisinin, and methotrexate. These pharmaceuticals demonstrated diverse anticancer actions, rendering them valuable tools in the therapy of OSCC. This review provides a comprehensive overview of molecular signaling in the reprocessing of drugs for OSCC.

This study investigates the potential of the compound 5,7-dimethoxyflavone (5,7-DMF) found in Piper ornatum as an anti-breast cancer agent using an in silico approach. The study targeted three major mechanisms involved in breast cancer progression: the ability of 5,7-DMF to inhibit kinase activity, act as a competitive inhibitor of cyclooxygenase 2 (COX-2) and nitric oxide synthase 2 (NOS2). This was investigated through molecular simulation by assessing drug-likeness, toxicity, membrane permeability, bioactivity, specific docking with AutoDock Vina integrated with PyRx 8.0, as well as molecular dynamics simulation using CABS-flex 2.0. Molecular docking results showed that 5,7-DMF has a high binding affinity towards the COX-2 target and inhibits kinase activity. This study also revealed significant interactions between 5,7-DMF and the COX-2 active site, supporting its potential as an anti-breast cancer agent. These results provide a solid basis for the further development of 5,7-DMF as a potential drug candidate against breast cancer.

Peripheral neuropathy (PN) is a common side effect of docetaxel (DTX). In this study, we aimed to evaluate the effects of montelukast (MNT), a leukotriene receptor antagonist drug, against DTX-induced PN in rats. Thirty-two male rats were divided into four groups and treated for four weeks: control (sham), DTX (5 mg/kg per week, ip), MNT (10 mg/kg per day, po), and DTX+MNT (5 mg/kg per week, ip + 10 mg/kg per day, po). Behavioral tests (hot plate, tail flick, and rotarod) were conducted. Histopathological, molecular (RT-PCR), and biochemical (ELISA) analyses were performed on sciatic nerve, liver, and serum samples. MNT reduced the malondialdehyde (MDA) levels and increased the superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) parameters in sciatic nerve tissues. Unlike DTX, MNT resulted in increased Bcl-2 gene expression and decreased caspase-3 (Cas-3) and Bax expressions. DTX caused sensory and motor neuropathy, as revealed by the hot plate, tail flick, and rotarod tests. The co-administration of MNT significantly mitigated the sensory and motor neuropathy induced by DTX. MNT improved the levels of NCAM, p38α MAPK, and nuclear factor kappa B (NF-κB), which were impaired in the sciatic nerve tissues due to DTX administration. Additionally, it reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which had increased due to DTX. Histopathological examination revealed that DTX-related sciatic nerve damage was mitigated by MNT administration. The results indicated that MNT may have a protective effect against DTX-induced PN in rats.