This study aimed to investigate the pharmacological mechanisms of Shugan Jianpi Formula (SGJPF) in treating TNBC using network pharmacology and molecular biology approaches.

Combination of multiple therapies is a common approach to treating patients with unresectable hepatocellular carcinoma (uHCC). The impact of immune checkpoint inhibitors (ICIs) on prognosis in uHCC patients treated with transarterial chemoembolization (TACE) and lenvatinib remains unclear.

Immune checkpoint inhibitors (ICIs) significantly improve survival in lung cancer patients. However, checkpoint inhibitor pneumonitis (CIP) remains a critical safety concern. This meta-analysis systematically evaluates demographic, clinical, and laboratory risk factors associated with CIP development to guide risk-stratified management.

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, particularly in lung cancer. However, their use in patients with pre-existing autoimmune diseases (PADs) presents unique challenges. PADs, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis, complicate the clinical management of lung cancer due to concerns about worsening autoimmune symptoms during ICI therapy. This review summarized the safety and efficacy of ICIs in lung cancer patients with PAD, focusing on the available clinical evidence, the optimal timing of ICI initiation, and the potential predictive biomarkers for immune-related adverse events (irAEs). Future prospective studies are needed to establish definitive guidelines for the use of ICIs in this population, with a focus on identifying patients at risk, managing ICI resumption after irAE and developing new medications with durable control of both cancer and PAD.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Many researchers have previously reported that natural compounds from plants or Chinese Traditional Herbs have a potential to treat NSCLC. But it has not been reported that phytol can treat NSCLC. In this research, we first exposed this effect on A549 cells and researched the mechanism.

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.

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.

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.

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.

Customizing drug treatments based on individual tumor susceptibility and patient-specific factors is a complex task, highlighting the need for better predictive models tailored to each patient. Preserving tumor architecture is one strategy to address the intricate interactions between stromal cells and tumor cell populations within a patient. In this study, we explored the feasibility of using pretherapeutic endoscopic tissue cultures from patients (ePDTCs) with gastric and esophagogastric junction cancers to assess individual drug susceptibility. We treated these endoscopic tissue slice cultures with 5-FU (1 µM), a modified FLOT regimen comprising 5-FU (10 µM), leucovorin (10 µM), oxaliplatin (20 µM), and docetaxel (0.1 µM), the active metabolite of irinotecan (SN38, at 1 µM and 10 µM) and the PD-1 inhibitor nivolumab (3 µg/ml). Analysis of the tumor tissue revealed stable adaptations to the culture environment, which were further enhanced by adding 2% autologous human serum to the culture media. Dose-dependent responses were observed with SN38 across all samples and individual susceptibility at low concentrations. Both 5-FU and the FLOT regimen as well as PD-1 inhibition, tested at bioavailable dosages, further demonstrated individualized responses in ePDTCs. This study shows that ePDTCs can effectively assess tissue susceptibility to drugs, warranting further investigation in larger cohorts to validate this model's potential alongside clinical treatments.

Pancreatic ductal adenocarcinoma (PDAC) is a cancer with dismal prognosis due to resistance to most current therapies. Although immunotherapy has improved the treatment of many solid cancers, pancreatic cancer remains resistant to immunotherapy due to immunosuppressive tumor microenvironment, limited lymphocyte infiltration and lack of neoantigens. Oncolytic adenoviruses are a possible solution to treatment resistance in PDAC due to their ability to elicit lymphocyte trafficking and epitope spreading. Herein, we tested if an oncolytic adenovirus encoding a variant interleukin-2 molecule (Ad5/3-E2F-d24-vIL2), could enable immune checkpoint inhibitor (ICI) therapy in PDAC when combined with chemotherapy. Rationale for Ad5/3-E2F-d24-vIL2 was tested in vitro, where increase in programmed death ligand 1 (PD-L1) expression was seen after virotherapy and chemotherapy. Expression of other B7 family proteins was characterized in mono- and co-culture settings of cancer cells, fibroblasts, and macrophages. The combination therapy of virotherapy, chemotherapy and ICI was characterized in freshly resected ex vivo pancreatic tumor samples. Combination of ICI with virotherapy showed increased interferon and chemokine production in samples, with expansion of cytotoxic CD8 + T cells seen by flow cytometry. In vivo evaluation of the triple combination therapy in a Syrian hamster model showed improved tumor growth control and overall survival, with concurrent increase in intratumoral lymphocytes during therapy. Animals cured with the therapy showed resistance to re-challenge with the same cell line, supportive of successful generation of anti-tumor immunity in the animals. The combination treatment of Ad5/3-E2F-d24-vIL2, chemotherapy, and checkpoint inhibition is a promising treatment modality to tackle treatment resistance in PDAC.