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.

The exploration of anticancer drugs has aimed at more effective, adaptable, and less harmful treatments, with natural products pivotal in cancer research. In addition to experimental techniques for identifying anticancer drug candidates, computational methods have been developed to virtually screen for potential anticancer compounds. This study introduces DFT_ANPD, a deep-learning framework for predicting anticancer properties in natural compounds by integrating molecular structural information with embeddings generated by large language models (LLMs). Its architecture combines structural and semantic insights to form enriched molecular representations. SMILES strings are processed by a 1D-CNN to uncover intricate chemical patterns, while a fine-tuned SMILES-BERT extracts semantic information. A two-sided attention mechanism fuses these features, selectively prioritizing chemically relevant features for a holistic molecular representation. Based on this comprehensive embedding, a sigmoid activation function predicts anticancer potential. Benchmarked against iANP-EC with the NPACT and CancerHSP datasets, DFT_ANPD demonstrated superior performance in AUC-ROC, AUC-PR, balanced accuracy, and MCC. Its generalization ability was further validated using the independent NPASS dataset, identifying and ranking the top 10 compounds with the highest anticancer potential, including the FDA-approved dactinomycin. Docking analysis of NPC479359, the sixth-ranked compound, revealed significant binding affinities with top five cancer-related proteins, such as the CB2 receptor and DNA lyase. These results underscore DFT_ANPD's utility in accelerating anticancer drug discovery across experimental-computational pipelines.

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.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by demonstrating significant efficacy across multiple malignancies. However, by interfering with immune regulatory pathways, they can lead to immune-related adverse events (irAEs), including immune-mediated enterocolitis. This study aimed to evaluate the real-world risk of immune-mediated enterocolitis across different ICIs using data from the FDA's Adverse Event Reporting System (FAERS).

An electrically controlled, programmable drug delivery system offers substantial potential in personalized biomedical devices. Current methods lack precise control over drug amounts and sequences, which is crucial for optimizing therapy. We present a solution with drug molecules modified onto gallium-based liquid metal nanoparticles (LMNPs) and using the electrochemical corrosion of LMNPs to controllably release the drugs, which allows arbitrary choice of drug types, release speed (fastest at less than 1 second), and sequence of release for customized therapy. This system applies to many types of drugs (molecules containing amine, thiol, hydroxyl, and carboxyl groups) and is integrated onto a stretchable thin film and can be implemented as epidermal or implantable devices. We tested the platform with antibiotics for wound infections and an antitumor drug for subcutaneous melanoma, confirming its excellent therapeutic efficacy and biocompatibility in both in vivo and in vitro tests.

Low-dose methotrexate (MTX) is the first-line drug for treating rheumatoid arthritis as an immunosuppressor. We have identified that low-dose MTX exhibits antitumor immune activity. MTX treatment reduced tumor metastasis and enhanced the efficacy of radiation therapy and immune checkpoint blockade therapy in mice. Mechanistically, MTX selectively induced DNA damage, cGAS-STING [cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING)] pathway activation, and cGAMP generation in cancer cells. Furthermore, MTX bound to the substrate-binding pocket of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), inhibiting ENPP1-mediated cGAMP hydrolysis and adenosine generation. Consequently, MTX reduced extracellular adenosine and enhanced host STING-mediated antitumor immunity. In addition, a preliminary clinical trial demonstrated promising efficacy and safety of low-dose MTX in combination with immunotherapy and radiotherapy for patients with unresectable or metastatic solid tumors, showing improved outcomes compared with historical controls. These results highlight the previously unrecognized immunostimulatory functions of MTX and provide a rationale for combining MTX with tumor immunotherapy and radiotherapy in clinical settings.

Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized.